Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue

Oben, Julius Enyong; Morgan, Linda; Fletcher, J. M.; Marks, Vincent

doi:10.1677/joe.0.1300267

Cited by 180 publications

(89 citation statements)

References 18 publications

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“…Thus, substantial differences exist between GIP actions in obesity as opposed to normal physiology, emphasising an important pathophysiological role of GIP. Adipocyte GIP receptors may be especially important, as GIP has been shown to promote fatty acid uptake and lipogenesis [25,26]. Since ob/ob mice exhibit leptin deficiency and low sympathetic activity [42], we cannot rule out additional effects, such as increased sympathetic activity and fatty acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…The GIP receptor is expressed in various extrapancreatic sites, including adipose tissue, bone, intestine, heart, stomach and brain [20]. In relation to this, GIP has been shown to inhibit gastric acid secretion [21], attenuate glucagon-stimulated glucose production [22], decrease hepatic insulin extraction [23] stimulate glucose uptake in muscle [24] and increase both fatty acid synthesis and lipoprotein lipase activity in adipocytes [25,26]. The particularly potent stimulation of GIP secretion after high-fat feeding [27] suggests a role for GIP in fat metabolism [20].…”

Section: Introductionmentioning

confidence: 99%

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Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

et al. 2007

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Aims/hypothesis Ablation of gastric inhibitory polypeptide (GIP) receptor action is reported to protect against obesity and associated metabolic abnormalities. The aim of this study was to use prediabetic ob/ob mice to examine whether 60 days of chemical GIP receptor ablation with (Pro 3 )GIP is able to counter the development of genetic obesityrelated diabetes. Materials and methods Young (5-7 weeks) ob/ob mice received once daily i.p. injections of either saline vehicle or (Pro 3 )GIP (25 nmol kg −1 day −1 ) over a 60 day period. Food intake, body weight and circulating glucose and insulin were measured at frequent intervals. At 60 days, glucose tolerance, response to native GIP, postprandial responses, insulin sensitivity, HbA 1c , circulating hormones and plasma lipids were assessed. Results Body weight and food intake in (Pro 3 )GIP-treated mice did not differ from ob/ob controls. GIP receptor blockade significantly improved non-fasting glucose (p< 0.001), HbA 1c (p<0.05), glucose tolerance (p<0.001), meal tolerance (p<0.001) and insulin sensitivity (p<0.05). Remarkably, (Pro 3 )GIP treatment prevented the age-related development of diabetes, as none of these parameters differed significantly between treated ob/ob mice and normal age-matched lean controls. Circulating levels of glucagon, corticosterone, adiponectin and total cholesterol were unchanged by (Pro 3 )GIP, while levels of triacylglycerol, LDLcholesterol and resistin were decreased (p<0.05) compared with those in control ob/ob mice. Plasma and pancreatic insulin concentrations were generally lower after (Pro 3 )GIP treatment than in control ob/ob mice (p<0.01), but plasma insulin levels remained substantially raised (p<0.001) compared with those observed in lean controls. Conclusions/interpretation These data indicate that sustained GIP receptor antagonism provides an effective means of preventing the development of many of the metabolic abnormalities of obesity-driven diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

et al. 2007

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“…The physiological function of GIP plays a key role in promoting fatty acid incorporation and synthesis 7, 8 and enhancing of lipoprotein lipase (LPL) activity in explant adipose tissues or 3 T3‐L1 cell 9, 10. Increased postprandial GIP levels have been associated with obesity in both human 11, 12, 13, 14, 15 and mice 16.…”

Section: Introductionmentioning

confidence: 99%

Gastric inhibitory polypeptide receptor antagonist, SKL‐14959, suppressed body weight gain on diet‐induced obesity mice

Nakamura¹,

Tanimoto²,

Mizuno³

et al. 2018

Obesity Science & Practice

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SummaryObjectiveGastric inhibitory polypeptide plays a role in glucose and lipid metabolism and is associated with obesity and insulin resistance. The objective of this study is to confirm the anti‐obesity effects of the gastric inhibitory polypeptide receptor antagonist, SKL‐14959, on diet‐induced obesity mice.MethodDiet‐induced obesity mice at 20 weeks of age were administered with or without SKL‐14959 for 96 d. Body weight and food intake were monitored throughout the experiment. Mice were sacrificed, and physiological and biochemical markers were measured, and then histochemical and gene expression analyses were also performed. In further studies, mice were orally gavaged with [14C]‐oleic acid to investigate the excursion of digested lipids.ResultsSKL‐14959 significantly suppressed weight gain without affecting food intake, decreased triacylglycerol contents in the liver and the muscle and the intensity stained with oil‐red in the liver. It also improved plasma glutamic pyruvic transaminase and 3‐hydroxybutyrate levels in addition to notably down‐regulated relative gene expression of srebf1 and dgat1 in the liver despite not altering in the adipose tissue. Furthermore, SKL‐14959 showed remarkable inhibition of lipid uptake in the adipose tissue after the oil challenge.ConclusionSKL‐14959 inhibited lipids uptake and improved lipids metabolism, results in suppression of body‐weight gain.

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“…Increased GLP-1 levels may account for the enhanced first and second phase of insulin secretion in AA and the exacerbated insulin response in obese subjects. GLP-1 promotes adipogenesis through its effects on insulin sensitivity, stimulation of fatty acid synthesis in adipose tissue 9 and attenuation of the lipolytic action of glucagons. 10,11 Obese animals and humans have increased GLP-1 concentrations in response to fat and glucose intake 1,12,13 and an exacerbated insulin secretion in response to lower concentration of GLP-1.…”

Section: Discussionmentioning

confidence: 99%

Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults

et al. 2004

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OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR s Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct b-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. IntroductionHyperinsulinemia is the hallmark of obesity and several of the obesity-related diseases including type II diabetes mellitus (T2DM) and cardiovascular disease (CVD). Whether the hyperinsulinemia is primary or secondary to obesity is still in debate. African-Americans (AA) have a higher prevalence of obesity, T2DM and CVD, and higher resting and stimulated insulin concentrations than obese Caucasians, which cannot be explained by the severity of obesity or the degree of insulin sensitivity. The enteroinsular axis (EIA) is responsible for 450% of the postprandial insulin release, and glucagon-like peptide-1 (GLP-1) is the major determinant of early insulin secretion in response to a mixed meal. 1 It has been suggested that the somatostatin analogue, octreotide, decreases glucose-stimulated insulin response in a dose-dependent way through a specific subset of somatostatin receptors on pancreatic b cells. [2][3][4][5] This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR s Depot; Novartis) on the EIA in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct b-cell effect and through mediating GLP-1 response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. Materials and methods

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Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue

Cited by 180 publications

References 18 publications

Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

Gastric inhibitory polypeptide receptor antagonist, SKL‐14959, suppressed body weight gain on diet‐induced obesity mice

Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults

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