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Glucose-dependent Insulinotropic Polypeptide (glucose-dependent + insulinotropic_polypeptide)
Selected AbstractsGlucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion-affected expression, and impaired regenerative axonal growthJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009Bettina A. Buhren Abstract Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice. © 2009 Wiley-Liss, Inc. [source] RD Lawrence Lecture 2008 Targeting GLP-1 release as a potential strategy for the therapy of Type 2 diabetesDIABETIC MEDICINE, Issue 8 2008F. M. Gribble Abstract Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal hormones that play an important role in stimulating postprandial insulin release from pancreatic ,-cells. Agents that either mimic GLP-1 or prevent its degradation are now available for the treatment of Type 2 diabetes, and strategies to enhance endogenous GLP-1 release are under assessment. As intestinal peptides have a range of actions, including appetite regulation and coordination of fat metabolism, harnessing the enteric endocrine system is a promising new field for drug development. [source] Incretins and other peptides in the treatment of diabetesDIABETIC MEDICINE, Issue 3 2007J. F. Todd Abstract Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially, which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. Patients with Type 2 diabetes have greatly impaired or absent incretin-mediated insulin secretion which is mainly as a result of decreased secretion of GLP-1. However, the insulinotropic action of GLP-1 is preserved in patients with Type 2 diabetes, and this has encouraged attempts to treat Type 2 diabetic patients with GLP-1. GLP-1 also possesses a number of potential advantages over existing agents for the treatment of Type 2 diabetes. In addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion, delays gastric emptying and inhibits food intake. Continuous intravenous and subcutaneous administration significantly improves glycaemic control and causes reductions in both HbA1c and body weight. However, GLP-1 is metabolized extremely rapidly in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). This is the probable explanation for the short-lived effect of single doses of native GLP-1, making it an unlikely glucose-lowering agent. The DPP-IV resistant analogue, exenatide, has Food and Drug Administration (FDA) approval for the treatment of Type 2 diabetes and selective DPP-IV inhibitors are under development. Both approaches have demonstrated remarkable efficacy in animal models and human clinical studies. Both are well tolerated and appear to have advantages over current therapies for Type 2 diabetes, particularly in terms of the effects on pancreatic B-cell restoration and potential weight loss. [source] Role of Gastrointestinal Hormones in Postprandial Reduction of Bone Resorption,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003Dennis B Henriksen Abstract Collagen type I fragments, reflecting bone resorption, and release of gut hormones were investigated after a meal. Investigations led to a dose escalation study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a dose-dependent effect of GLP-2 on the reduction of bone resorption. Introduction: The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX) can be used to assess bone resorption. This marker of bone resorption has a significant circadian variation that is influenced by food intake. However, the mediator of this variation has not been identified. Materials and Methods: We studied the release of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the intestinal proglucagon-derived peptides) after ingestion of glucose, fat, protein, and fructose, as well as their effects after parenteral administration in relation to bone turnover processes in healthy volunteers. Furthermore, we studied the effect on bone turnover of a single subcutaneous injection of GLP-2 in four different dosages (100, 200, 400, or 800 ,g GLP-2) or placebo in 60 postmenopausal women (mean age, 61 ± 5 years). Results: All macronutrients significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39,52% from baseline), and only the glucagon-like peptides were secreted in parallel. Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05). Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by 25% from baseline in the 800-,g GLP-2 group (p < 0.01). An area under the curve (AUC0,8h) analysis for s-CTX after GLP-2 injection confirmed the dose-dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by the GLP-2 treatment. Conclusion: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal. The dose-dependent reduction of bone resorption markers found after subcutaneous injection of GLP-2 warrants further investigation into the mechanism and importance of GLP-2 for the bone turnover processes. [source] Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgeryJOURNAL OF DIABETES, Issue 1 2010Mousumi BOSE Abstract Background:, The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose. Methods:, Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion. Results:, The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of ,-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. Conclusions:, The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery. [source] The identification of QTL that affect the fatty acid composition of milk on sheep chromosome 11ANIMAL GENETICS, Issue 3 2010M. García-Fernández Summary In this work, we analysed 11 genetic markers localized on OAR11 in a commercial population of Spanish Churra sheep to detect QTL that underlie milk fatty acid (FA) composition traits. Following a daughter design, we analysed 799 ewes distributed in 15 half-sib families. Eight microsatellite markers and three novel SNPs identified in two genes related to fatty acid metabolism, acetyl-CoA carboxylase , (ACACA) and fatty acid synthase (FASN), were genotyped in the whole population under study. The phenotypic traits considered in the study included 22 measurements related to the FA composition of the milk and three other milk production traits (milk protein percentage, milk fat percentage and milk yield). Across-family regression analysis revealed four significant QTL at the 5% chromosome-wise level influencing contents of capric acid (C10:0), lauric acid (C12:0), linoleic conjugated acid (CLA) and polyunsaturated fatty acids (PUFA) respectively. The peaks of the QTL affecting C10:0 and PUFA contents in milk map close to the FASN gene, which has been evaluated as a putative positional candidate for these QTL. The QTL influencing C12:0 content reaches its maximum significance at 58 cM, close to the gene coding for the glucose-dependent insulinotropic polypeptide. We were not able to find any candidate genes related to fat metabolism at the QTL influencing CLA content, which is located at the proximal end of the chromosome. Further research efforts will be needed to confirm and refine the QTL locations reported here. [source] Comparisons of leptin, incretins and body composition in obese and lean patients with hypopituitarism and healthy individualsCLINICAL ENDOCRINOLOGY, Issue 1 2003H. Mersebach Summary objective To identify possible abnormalities specific for obesity in hypopituitary patients. study design Cross-sectional case,control study. measurements and study subjects Body composition (DEXA) and measurements of fasting plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptides (GLPs), insulin, C-peptide, glucose, leptin and lipids were performed in 25 hypopituitary patients (15 obese, 10 normal weight) and 26 BMI and age-matched healthy controls (16 obese, 10 normal weight). All hypopituitary patients had GH deficiency and received adequate substitution therapy on this and other deficient axes (3 ± 1). results Fasting GIP-levels were significantly higher in obese hypopituitary patients compared to lean hypopituitary patients (P < 0·01), while the fasting concentrations of GLP-1 and GLP-2 were comparable between obese and lean hypopituitary patients. The same trend was seen in obese healthy controls vs. lean controls. No differences were observed in glucose, insulin or C-peptide between the hypopituitary patients and the controls. Leptin levels were increased in obese hypopituitary patients compared to lean hypopituitary patients when adjusted for gender. At least a 2-fold higher level of leptin was observed in women compared to men in both patient groups and healthy controls. Lean female hypopituitary patients had higher leptin levels than matched controls. conclusions Fasting levels of GIP were elevated in obese substituted hypopituitary patients, while fasting concentrations of GLPs were similar. Obese hypopituitary patients had the same degree of hyperinsulinaemia, affected glucose tolerance, dyslipoproteinaemia and central obesity as obese healthy controls. Further studies are required to identify the possible biochemical reasons for obesity in patients with apparently well-substituted hypopituitarism. [source] | |||||||||||||