Beta Amyloid Peptide: gastric inhibitory peptide | What is gastric inhibitory peptide|Papers ongastric inhibitory peptide |Research on gastric inhibitory peptide | Publica

gastric inhibitory peptide | What is gastric inhibitory peptide|Papers ongastric inhibitory peptide |Research on gastric inhibitory peptide | Publica

    Results: 1 to 20 of 2931

    1.
    Mol Nutr Food Res. 2011 Dec 7. doi: 10.1002/mnfr.201100381. [Epub ahead of print]

    Acute effect of whey peptides upon blood pressure of hypertensive rats, and relationship with their angiotensin-converting enzyme inhibitory activity.

    Source

    Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.

    Abstract

    Scope: The aim of this study was to investigate the antihypertensive effect of a peptide fraction (PepC) obtained from a whey protein concentrate following hydrolysis by Cynara cardunculus, as well as of its fraction with MW below 3 kDa (PepCF). Both these concentrates encompassed peptides that exhibited potent in vitro inhibition of angiotensin-converting enzyme (ACE): two were released from α-lactalbumin - KGYGGVSLPEW and DKVGINYW, and one from β-lactoglobulin - DAQSAPLRVY. Methods and results: Upon oral administration, by gastric intubation, of 400 mg/kg body weight (bw) of those peptide concentrates, or 5 mg/kg bw of the corresponding synthetic peptides, to 12 wk-old spontaneously hypertensive rats (SHR), the systolic and diastolic blood pressures were monitored by the tail-cuff method - before, and 2, 4, 6, 8 and 24 h afterwards. Water and zofenopril (5 mg/kg bw) - a known ACE-inhibitor, were used as negative and positive controls, respectively. Acute administration of PepC, PepCF, KGYGGVSLPEW, DKVGINYW and DAQSAPLRVY caused antihypertensive effects in SHR; the maximum effect occurred by 4 h and 6 h after administration of the peptide concentrates and the synthetic peptides, respectively. PepC and KGYGGVSLPEW also showed ACE-inhibitory activity in vivo: the pressor effect of angiotensin I was significantly lower, and the response to bradykinin increased when the rats were pre-treated with either product. Conclusion: Our results strongly suggest that PepC will be effective as nutraceutical ingredient for the formulation of functional foods aimed at hypertension control.

    Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    PMID:
    22147557
    [PubMed - as supplied by publisher]
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    2.
    Mol Pharmacol. 2011 Nov 22. [Epub ahead of print]

    Lateral Allosterism in the Glucagon Receptor Family: GLP-1 Induces GPCR Heteromer Formation.

    Source

    Addex Pharmaceuticals.

    Abstract

    Activation of a G-protein coupled receptor (GPCR) results in a variety of cellular responses, for example, through binding of different ligands to the same receptor that activate distinct downstream cascades. Additional signaling complexity is achieved when two or more receptors are integrated into one signaling unit. Lateral receptor interactions can allosterically modulate the receptor response to a ligand thereby create a mechanism of tissue specific fine tuning, depending on the cellular receptor co-expression pattern. GPCR homo- or heteromers have been explored widely in GPCR class A and C, but to lesser extent in class B. In the present study, we used Bioluminescence Resonance Energy Transfer (BRET) techniques, calcium flux measurements, and microscopy to study receptor interactions within the glucagon receptor family. We found basal BRET interactions in some of the receptor combinations tested that decreased upon ligand binding. A BRET increase was exclusively observed between the gastric-inhibitory-peptide-receptor (GIPR) and the glucagon-like-peptide-1-receptor (GLP 1R) upon binding of GLP-1, and could be reversed by GIP addition. The interactions of GLP-1R and GIPR were characterized by BRET-donor saturation studies, shift experiments, and testing of glucagon-like ligands. The heteromer displayed a specific pharmacology in GLP-1 induced β-arrestin recruitment and calcium flux, suggesting a form of allosteric regulation between the receptors. This study provides the first example of ligand-induced heteromer formation in GPCR class B. In the body, both receptors are functionally related and co-expressed in the same cells. The physiological evidence of this heteromerization remains to be determined.

    PMID:
    22108912
    [PubMed - as supplied by publisher]
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    3.
    Am J Physiol Gastrointest Liver Physiol. 2011 Nov 10. [Epub ahead of print]

    Glucagon-Like Peptide-1 Modulates Neurally-Evoked Mucosal Chloride Secretion in Guinea Pig Small Intestine In Vitro.

    Source

    1Universita' di Palermo.

    Abstract

    Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLR-1 effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current (Isc), which served as a marker for chloride secretion. Transmural EFS evoked neurally-mediated biphasic increases in Isc that had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in concentration-dependent manner. The GLP-1 receptor antagonist, exendin (9-39), suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic and vasoactive intestinalpeptide receptor antagonists, but not muscarinic antagonists. GLP-1 significantly reduced EFS-evoked release of ACh. In the submucosal plexus, GLP-1R-immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and its activation leads to a decrease in neurally-evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions and at nicotinic synapses in the enteric neural networks that control secretomotor funcions.

    PMID:
    22075777
    [PubMed - as supplied by publisher]
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    4.
    Surg Clin North Am. 2011 Dec;91(6):1149-61, vii.

    Physiology of weight loss surgery.

    Source

    Duke Endosurgery, Department of Surgery, Duke University, DUMC 3351, Duke University Medical Center, Durham, NC 27713, USA.

    Abstract

    The clinical outcomes achieved by bariatric surgery have been impressive. However, the physiologic mechanisms and complex metabolic effects of bariatric surgery are only now beginning to be understood. Ongoing research has contributed a large amount of data and shed new light on the science behind obesity and its treatment, and this article reviews the current understanding of metabolic and bariatric surgery physiology.

    Copyright © 2011 Elsevier Inc. All rights reserved.

    PMID:
    22054145
    [PubMed - indexed for MEDLINE]
    5.
    Diabetes Obes Metab. 2011 Nov 3. doi: 10.1111/j.1463-1326.2011.01526.x. [Epub ahead of print]

    Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients.

    Source

    Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan Jiyugaoka Medical Clinic, Internal Medicine, Obihiro, Japan Department of Metabolism and Clinical Nutrition, Akita University School of Medicine, Akita, Japan.

    Abstract

    To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy.

    © 2011 Blackwell Publishing Ltd.

    PMID:
    22051162
    [PubMed - as supplied by publisher]
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    6.
    Acta Histochem. 2011 Oct 28. [Epub ahead of print]

    Glucagon-like peptide 1 (GLP-1) in the gastrointestinal tract of the pheasant (Phasianus colchicus).

    Source

    Department of Physiological Science, University of Pisa, Pisa, Italy.

    Abstract

    The distribution of Glucagon-like peptide 1 (GLP-1) was investigated in the gastrointestinal tract of the pheasant using immunohistochemistry. GLP-1 immunoreactive cells were common in the small intestine, in the proventriculus and in the pancreas. Immunostained cells were not seen in the crop, in the gizzard and in the large intestine. Double labelling demonstrated that GLP-1 and pituitary adenylate cyclase-activating polypeptide (PACAP) were occasionally co-localized only in the duodenal villi. In contrast to what was previously described in the chicken and ostrich, we noted GLP-1 positive cells in the duodenum. These data were consistent with the presence of proglucagon mRNA in the chicken duodenum. Our findings indicate that GLP-1 might have an inhibitory effect on gastric and crop emptying and on acid secretion also in the pheasant. Moreover, the results of the present research regarding the initial region of the small intestine suggest a further direct mechanism of the GLP-1 release during the early digestion phase and an enhancement of its incretin role.

    Copyright © 2011 Elsevier GmbH. All rights reserved.

    PMID:
    22036174
    [PubMed - as supplied by publisher]
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    7.
    N Engl J Med. 2011 Oct 27;365(17):1597-604.

    Long-term persistence of hormonal adaptations to weight loss.

    Source

    Department of Medicine (Austin and Northern Health), University of Melbourne, Melbourne, VIC, Australia.

    Abstract

    BACKGROUND:

    After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.

    METHODS:

    We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.

    RESULTS:

    Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).

    CONCLUSIONS:

    One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

    PMID:
    22029981
    [PubMed - indexed for MEDLINE]
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    8.
    J Biol Chem. 2011 Dec 16;286(50):43062-70. Epub 2011 Oct 25.

    Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase.

    Source

    From the Departments of Biochemistry.

    Abstract

    Gastric inhibitory peptide (GIP) is an incretin hormone secreted in response to food intake. The best known function of GIP is to enhance glucose-dependent insulin secretion from pancreatic β-cells. Extra-pancreatic effects of GIP primarily occur in adipose tissues. Here, we demonstrate that GIP increases insulin-dependent translocation of the Glut4 glucose transporter to the plasma membrane and exclusion of FoxO1 transcription factor from the nucleus in adipocytes, establishing that GIP has a general effect on insulin action in adipocytes. Stimulation of adipocytes with GIP alone has no effect on these processes. Using pharmacologic and molecular genetic approaches, we show that the effect of GIP on adipocyte insulin sensitivity requires activation of both the cAMP/protein kinase A/CREB signaling module and p110β phosphoinositol-3' kinase, establishing a novel signal transduction pathway modulating insulin action in adipocytes. This insulin-sensitizing effect is specific for GIP because isoproterenol, which elevates adipocyte cAMP and activates PKA/CREB signaling, does not affect adipocyte insulin sensitivity. The insulin-sensitizing activity points to a more central role for GIP in intestinal regulation of peripheral tissue metabolism, an emerging feature of inter-organ communication in the control of metabolism.

    PMID:
    22027830
    [PubMed - in process]
    PMCID: PMC3234864
    [Available on 2012/12/16]
    Click here to read
    9.
    Surg Obes Relat Dis. 2011 Nov-Dec;7(6):683-90. Epub 2011 Jul 31.

    Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy.

    Source

    Department of Surgery, Min-Sheng General Hospital, Taoyuan, Taiwan.

    Abstract

    BACKGROUND:

    Laparoscopic gastric bypass (GB) is reportedly more effective than laparoscopic sleeve gastrectomy (SG) in the treatment of patients with a low body mass index and type 2 diabetes mellitus. However, the mechanism remains speculative. We compared the postprandial gut hormone patterns between patients undergoing laparoscopic GB and laparoscopic SG at 2 years after surgery in a hospital-based, prospective study.

    METHODS:

    A total of 16 laparoscopic GB and 16 laparoscopic SG patients were followed up and appraised for glucose homeostasis. Two years after surgery, the mixed meal test and gut hormones were evaluated in 13 laparoscopic GB and 13 laparoscopic SG patients who had been included in the previous randomized trial.

    RESULTS:

    The preoperative characteristics, such as body mass index, body weight, waist circumference, and duration of T2DM were comparable between the 2 groups. T2DM remission was achieved in 13 (81%) laparoscopic GB and 3 (19%) laparoscopic SG patients (P < .05) 2 years after surgery. The laparoscopic GB patients had lost more weight and had a smaller waist circumference and lower levels of glucose and hemoglobin A1c, and lower insulin resistance than the SG patients. Significant differences were found in acyl ghrelin, des-acyl ghrelin, cholecystokinin, and resistin between the 2 groups, but none in obestatin, gastric inhibitory peptide, glucagon-like peptide-1, and leptin.

    CONCLUSIONS:

    Both laparoscopic GB and laparoscopic SG have strong hindgut effects after surgery, but GB has a significant duodenal exclusion effect on cholecystokinin. The laparoscopic SG group had lower acyl ghrelin and des-acyl ghrelin levels but greater concentrations of resistin than the laparoscopic GB group.

    Copyright © 2011 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

    PMID:
    21996600
    [PubMed - in process]
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    10.
    Clin Pharmacol Ther. 2011 Nov;90(5):685-92. doi: 10.1038/clpt.2011.169. Epub 2011 Oct 5.

    Pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-38431055, a novel GPR119 receptor agonist and potential antidiabetes agent, in healthy male subjects.

    Source

    Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Spring House, Pennsylvania, USA. LKatz3@its.jnj.com

    Abstract

    The incidence of type 2 diabetes mellitus is increasing worldwide. Several G-protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The terminal elimination half-life was ~13 h when administered as an oral suspension formulation. JNJ-38431055 was well tolerated and was not associated with hypoglycemia. As compared with placebo, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-likepeptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans.

    PMID:
    21975348
    [PubMed - indexed for MEDLINE]
    Click here to read
    11.
    Int J Obes (Lond). 2011 Sep;35 Suppl 3:S22-5. doi: 10.1038/ijo.2011.143.

    Diabetes remission after bariatric surgery: is it just the incretins?

    Source

    New York Obesity Nutrition Research Center, Division of Endocrinology and Diabetes, Department of Medicine, St Luke's Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10025, USA. BBL14@columbia.edu

    Abstract

    Gastric bypass surgery (GBP) results in important and sustained weight loss and remarkable improvement of Type 2 diabetes. The favorable change in the incretin gut hormones is thought to be responsible, in part, for diabetes remission after GBP, independent of weight loss. However, the relative role of the change in incretins and of weight loss is difficult to differentiate. After GBP, the plasma concentrations of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide increase postprandially by three- to fivefold. The postprandial incretin effect on insulin secretion, blunted in diabetes, improves rapidly after the surgery. In addition to the change in incretins, the pattern of insulin secretion in response to oral glucose changes after GBP, with recovery of the early phase and significant decrease in postprandial glucose levels. These changes were not seen after an equivalent weight loss by diet. The improved insulin release and glucose tolerance after GBP were shown by others to be blocked by the administration of a GLP-1 antagonist, demonstrating that the favorable metabolic changes after GBP are, in part, GLP-1 dependent. The improved incretin levels and effect persist years after GBP, but their long-term effect on glucose metabolism, and on hypoglycemia post GBP are yet unknown. Understanding the mechanisms by which incretin release is exaggerated postprandially after GBP may help develop new less invasive treatment options for obesity and diabetes. Changes in rate of eating, gastric emptying, intestinal transit time, nutrient absorption and sensing, as well as bile acid metabolism, may all be implicated.

    PMID:
    21912382
    [PubMed - indexed for MEDLINE]
    Click here to read
    12.
    Diabetologia. 2012 Jan;55(1):94-104. Epub 2011 Sep 16.

    A common variant upstream of the PAX6 gene influences islet function in man.

    Source

    Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, CRC at Skåne University Hospital, 205 02, Malmö, Sweden, Emma.Ahlqvist@med.lu.se.

    Abstract

    AIMS/HYPOTHESIS:

    Impaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1. We investigated whether a common PAX6 variant would mimic these findings and explored in detail its effect on islet function in man.

    METHODS:

    A PAX6 candidate single nucleotide polymorphism (rs685428) was associated with fasting insulin levels in the Diabetes Genetics Initiative genome-wide association study. We explored its potential association with glucose tolerance and insulin processing and secretion in three Scandinavian cohorts (N = 8,897 individuals). In addition, insulin secretion and the expression of PAX6 and transcriptional target genes were studied in human pancreatic islets.

    RESULTS:

    rs685428 G allele carriers had lower islet mRNA expression of PAX6 (p = 0.01) and PCSK1 (p = 0.001) than AA homozygotes. The G allele was associated with increased fasting insulin (p (replication) = 0.02, p (all) = 0.0008) and HOMA-insulin resistance (p (replication) = 0.02, p (all) = 0.001) as well as a lower fasting proinsulin/insulin ratio (p (all) = 0.008) and lower fasting glucagon (p = 0.04) and gastric inhibitory peptide (GIP) (p = 0.05) concentrations. Arginine-stimulated (p = 0.02) insulin secretion was reduced in vivo, which was further reflected by a reduction of glucose- and potassium-stimulated insulin secretion (p = 0.002 and p = 0.04, respectively) in human islets in vitro.

    CONCLUSIONS/INTERPRETATION:

    A common variant in PAX6 is associated with reduced PAX6 and PCSK1 expression in human islets and reduced insulin response, as well as decreased glucagon and GIP concentrations and decreased insulin sensitivity. These findings emphasise the central role of PAX6 in the regulation of islet function and glucose metabolism in man.

    PMID:
    21922321
    [PubMed - in process]
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    13.
    Cent Nerv Syst Agents Med Chem. 2011 Sep 1;11(3):210-22.

    Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival.

    Source

    Istituto di Scienze Neurologiche, CNR, Via Paolo Gaifami, 18, 95125 Catania, Italy. s.cavallaro@isn.cnr.it.

    Abstract

    The development of neuronal apoptosis depends on an intrinsic transcriptional program. By DNA microarray technology, we have previously implicated a number of genes in different paradigms of neuronal apoptosis. In the present study, we investigated the spatiotemporal pattern of expression of two of these genes, gastric inhibitory polypeptide (Gip) and its receptor (Gipr) in the rat central nervous system. The levels of their transcripts were measured with real-time quantitative polymerase chain reaction and in situ-hybridization. Widespread expression of Gip and Gipr was found in adult rat brain, whereas during postnatal cerebellum development, they were highly expressed in the external and internal granule layer, and in Purkinje cells. To investigate the possible biological function of Gip we examined its effects in vitro. Addition of Gip to cultured cerebellar granule neurons reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mM K+. This neurotrophic effect was mimicked by that of PACAP38 and IGF1. We conclude that Gip acts as an endogenous neurotrophic factor and supports neuronal survival.

    PMID:
    21919873
    [PubMed - in process]
    Click here to read
    14.
    Am J Physiol Endocrinol Metab. 2012 Jan;302(1):E43-51. Epub 2011 Sep 13.

    Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects.

    Source

    Steno Diabetes Center, Niels Steensens Vej 1, 2820 Gentofte, Denmark. charlotte.broens@rh.regionh.dk.

    Abstract

    Low birth weight (LBW) is associated with an increased risk of insulin resistance and downregulation of oxidative phosphorylation (OXPHOS) genes when exposed to a metabolic challenge of high-fat overfeeding (HFO). To elaborate further on the differential effects of HFO in LBW subjects, we measured in vivo mitochondrial function, insulin secretion, hepatic glucose production, and plasma levels of key regulatory hormones before and after 5 days of HFO in 20 young LBW and 26 normal-birth-weight (NBW) men. The LBW subjects developed peripheral insulin resistance after HFO due to impaired endogenous glucose storage (9.42 ± 4.19 vs. 5.91 ± 4.42 mg·kg FFM(-1)·min(-1), P = 0.01). Resting muscle phosphorcreatine and total ATP in muscle increased significantly after HFO in LBW subjects only, whereas additional measurements of mitochondrial function remained unaffected. Despite similar plasma FFA levels, LBW subjects displayed increased fat oxidation during insulin infusion compared with normal-birth-weight (NBW) subjects after HFO (0.37 ± 0.35 vs. 0.17 ± 0.33 mg·kg FFM(-1)·min(-1), P = 0.02). In contrast to NBW subjects, the plasma leptin levels of LBW subjects did not increase, and the plasma gastric inhibitory polypeptide (GIP) as well as pancreatic polypeptide(PP) levels increased less in LBW compared with NBW subjects during HFO. In conclusion, HFO unmasks dissociation between insulin resistance and mitochondrial dysfunction in LBW subjects, suggesting that insulin resistance may be a cause, rather than an effect, of impaired muscle OXPHOS gene expression and mitochondrial dysfunction. Reduced increments in response to HFO of fasting plasma leptin, PP, and GIP levels may contribute to insulin resistance, lower satiety, and impaired insulin secretion in LBW subjects.

    PMID:
    21917634
    [PubMed - in process]
    Click here to read
    15.
    Prog Biophys Mol Biol. 2011 Nov;107(2):286-92. Epub 2011 Sep 3.

    Cellular glucose availability and glucagon-like peptide-1.

    Source

    Department of Physiology, Keimyung University School of Medicine, 2800 Dalgubeoldae-Ro, Dalseo-Gu, Daegu 704-701, Republic of Korea.

    Abstract

    Glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide (GIP, glucose-dependent insulinotropic polypeptide) are produced in enteroendocrine L-cells and K-cells, respectively. They are known as incretins because they potentiate postprandial insulin secretion. Although unresponsiveness of type 2 diabetes (T2D) patients to GIP has now been reconsidered, GLP-1 mimetics and inhibitors of the GLP-1 degradation enzyme dipeptidyl peptidase (DPP)-4 have now been launched as drugs against T2D. The major roles of GLP-1 in T2D are reduction of appetite, gastric motility, glucagon secretion, enhancement of insulin secretion and β-cell survival. For insulin secretion and peripheral insulin function, GLP-1 and its mimetics sensitise β-cells to glucose; accelerate blood glucose withdrawal, in-cell glucose utilisation and glycogen synthesis in insulin-sensitive tissues; and assist in the function and survival of neurons mainly using glucose as an energy source. Taken together, GLP-1 acts to potentiate glucose availability of various cells or tissues to assist with their essential functions and/or survival. Herein, we review the signalling pathways and clinical relevance of GLP-1 in enhancing cellular glucose availability. On the basis of our recent research results, we also describe a mechanism that regulates GLP-1 for glucokinase activity. Because diabetic tissues including β-cells resist glucose, GLP-1 may be useful for treating T2D.

    Copyright © 2011 Elsevier Ltd. All rights reserved.

    PMID:
    21907232
    [PubMed - in process]
    Click here to read
    16.
    Biol Chem. 2011 Oct;392(10):909-18.

    Insulin modulates glucose-dependent insulinotropic polypeptide (GIP) secretion from enteroendocrine K cells in rats.

    Source

    SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, UK. n.irwin@ulster.ac.uk

    Abstract

    Effects of insulin excess and deficiency on glucose-dependent insulinotropic polypeptide (GIP) was examined in rats following insulinoma transplantation or streptozotocin (STZ) administration. Over 14 days, food intake was increased (p < 0.001) in both groups of rats, with decreased body weight (p < 0.01) in STZ rats. Non-fasting plasma glucose levels were decreased (p < 0.01) and plasma insulin levels increased (p < 0.001) in insulinoma-bearing rats, whereas STZ treatment elevated glucose (p < 0.001) and decreased insulin (p < 0.01). Circulating GIP concentrations were elevated (p < 0.01) in both animal models. At 14 days, oral glucose resulted in a decreased glycaemic excursion (p < 0.05) with concomitant elevations in insulin release (p < 0.001) in insulinoma-bearing rats, whereas STZ-treated rats displayed similar glucose-lowering effects but reduced insulin levels (p < 0.01). GIP concentrations were augmented in STZ rats (p < 0.05) following oral glucose. Plasma glucose and insulin concentrations were not affected by oral fat, but fat-induced GIP secretion was particularly (p < 0.05) increased in insulinoma-bearing rats. Exogenous GIP enhanced (p < 0.05) glucose-lowering in all groups of rats accompanied by insulin releasing (p < 0.001) effects in insulinoma-bearing and control rats. Both rat models exhibited increased (p < 0.001) intestinal weight but decreased intestinal GIP concentrations. These data suggest that circulating insulin has direct and indirect effects on the synthesis and secretion of GIP.

    PMID:
    21851286
    [PubMed - indexed for MEDLINE]
    Click here to read
    17.
    Am J Clin Nutr. 2011 Oct;94(4):997-1003. Epub 2011 Aug 17.

    Contributions of fat and protein to the incretin effect of a mixed meal.

    Source

    Department of Physiology, University of Lausanne, Lausanne, Switzerland.

    Abstract

    BACKGROUND:

    The relative contributions of fat and protein to the incretin effect are still largely unknown.

    OBJECTIVE:

    This study assessed the incretin effects elicited by a mixed meal, and by its fat and protein components alone, with the use of a hyperglycemic clamp combined with oral nutrients.

    DESIGN:

    Eight healthy volunteers were studied over 6 h after ingestion of a sandwich containing 1) dried meat, butter, and white bread; 2) dried meat alone; 3) butter alone; or 4) no meal (fasting control). Meals were ingested during a hyperglycemic clamp, and the incretin effect was calculated as the increment in plasma insulin after food intake relative to the concentrations observed during the control study.

    RESULTS:

    A significant augmentation of postprandial insulin secretion, independent of plasma glycemia, occurred after ingestion of the mixed nutrients and the lipid component of the mixed meal (203 ± 20.7% and 167.4 ± 22.9% of control, respectively; both P < 0.05), whereas the protein component did not induce a significant incretin effect (129.0 ± 7.9% of control; P = 0.6)

    CONCLUSIONS:

    Fat ingestion, in an amount typical of a standard meal, increases insulin secretion during physiologic hyperglycemia and thus contributes to the incretin effect. In contrast, ingestion of protein typical of normal meals does not contribute to the augmentation of postprandial insulin secretion. This trial was registered at clinicaltrials.gov as NCT00869453.

    PMID:
    21849595
    [PubMed - indexed for MEDLINE]
    Click here to read
    18.
    Diabetes Obes Metab. 2011 Oct;13 Suppl 1:69-81. doi: 10.1111/j.1463-1326.2011.01444.x.

    Incretin hormones and the expanding families of glucagon-like sequences and their receptors.

    Source

    Department of Laboratory Medicine and Pathobiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. david.irwin@utoronto.ca

    Abstract

    Peptide hormones encoded by the proglucagon (Gcg) and glucose-dependent insulinotropic polypeptide (Gip) genes are evolutionarily related glucagon-like sequences and act through a subfamily of G-protein-coupled receptors. A better understanding of the evolutionary history of these hormones and receptors should yield insight into their biological functions. The availability of a large number of near-complete vertebrate genome sequences is a powerful resource to address questions concerning the evolution of sequences; here, we utilize these resources to examine the evolution of glucagon-like sequences and their receptors. These studies led to the discovery of novel genes for a glucagon receptor-like receptor (Grlr) and a glucagon-like sequence (exendin) in vertebrates. Both exendin and GRLR have ancient origins, early in vertebrate evolution, but have been lost on the ancestral lineage leading to extant mammals. We also show that exendin and GRLR are both expressed in the brain of the chicken and Xenopus tropicals, results that suggest that the products of these genes function in this tissue. The lack of exendin or Grlr genes in mammals suggests that other genes may have acquired the functions of exendin and Grlr during mammalian evolution.

    © 2011 Blackwell Publishing Ltd.

    PMID:
    21824259
    [PubMed - indexed for MEDLINE]
    Click here to read
    19.
    Prog Biophys Mol Biol. 2011 Nov;107(2):248-56. Epub 2011 Jul 28.

    Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation.

    Source

    The Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima-ku, Osaka 553-0003, Japan. ydaisuke-kyoto@umin.ac.jp

    Abstract

    Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine upon ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family. Receptor binding activates and increases the level of intracellular cAMP in pancreatic β cells, thereby stimulating insulin secretion glucose-dependently. In addition to their insulinotropic effects, GIP and GLP-1 have been shown to preserve pancreatic β cell mass by inhibiting apoptosis of β cells and enhancing their proliferation. Due to such characteristics, incretin hormones have been gaining mush attention as attractive targets for treatment of type 2 diabetes, and indeed incretin-based therapeutics have been rapidly disseminated worldwide. However, despites of plethora of rigorous studies, molecular mechanisms underlying how GIPR and GLP-1R activation leads to enhancement of glucose-dependent insulin secretion are still largely unknown. Here, we summarize the similarities and differences of these two incretin hormones in secretion and metabolism, their insulinotropic actions and their effects on pancreatic β cell preservation. We then try to discuss potential of GLP-1 and GIP in treatment of type 2 diabetes.

    Copyright © 2011 Elsevier Ltd. All rights reserved.

    PMID:
    21820006
    [PubMed - in process]
    Click here to read
    20.
    PLoS One. 2011;6(7):e22814. Epub 2011 Jul 26.

    Postnatal development of numbers and mean sizes of pancreatic islets and beta-cells in healthy mice and GIPR(dn) transgenic diabetic mice.

    Source

    Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Germany. herbach@patho.vetmed.uni-muenchen.de

    Abstract

    The aim of this study was to examine postnatal islet and beta-cell expansion in healthy female control mice and its disturbances in diabetic GIPR(dn) transgenic mice, which exhibit an early reduction of beta-cell mass. Pancreata of female control and GIPR(dn) transgenic mice, aged 10, 45, 90 and 180 days were examined, using state-of-the-art quantitative-stereological methods. Total islet and beta-cell volumes, as well as their absolute numbers increased significantly until 90 days in control mice, and remained stable thereafter. The mean islet volumes of controls also increased slightly but significantly between 10 and 45 days of age, and then remained stable until 180 days. The total volume of isolated beta-cells, an indicator of islet neogenesis, and the number of proliferating (BrdU-positive) islet cells were highest in 10-day-old controls and declined significantly between 10 and 45 days. In GIPR(dn) transgenic mice, the numbers of islets and beta-cells were significantly reduced from 10 days of age onwards vs. controls, and no postnatal expansion of total islet and beta-cell volumes occurred due to a reduction in islet neogenesis whereas early islet-cell proliferation and apoptosis were unchanged as compared to control mice. Insulin secretion in response to pharmacological doses of GIP was preserved in GIPR(dn) transgenic mice, and serum insulin to pancreatic insulin content in response to GLP-1 and arginine was significantly higher in GIPR(dn) transgenic mice vs. controls. We could show that the increase in islet number is mainly responsible for expansion of islet and beta-cell mass in healthy control mice. GIPR(dn) transgenic mice show a disturbed expansion of the endocrine pancreas, due to perturbed islet neogenesis.

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