Gastric inhibitory polypeptide (GIP) suppression of hepatic glucose production

Andersen, DK; Putnam, WS; Hanks, JB; Wise, JE; Lebovitz, H. E.; Rs, Jones

doi:10.1016/0167-0115(80)90026-9

Cited by 9 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent data indicate that GIP also exerts an effect on hepatic glucose production. In dogs with chronic portal venous catheters, GIP reduced hepatic glucose output without a concomitant increase in plasma insulin [62]. In the isolated perfused rat liver, even pharmacological doses of GIP were unable to inhibit the glycogenolytic effect of glucagon.…”

Section: Direct Metabolic Effects Of Gipmentioning

confidence: 92%

New developments in the incretin concept

1985

View full text Add to dashboard Cite

Experimental and clinical work over the last 6 years has confirmed and broadened, but also challenged, the incretin concept. The nervous component of the entero-insular axis is still poorly defined, especially the peptidergic nerves, of which several contain insulinotropic regulatory peptides. The incretin effect is preserved after complete denervation of the porcine pancreas. Type 2 (non insulin-dependent) diabetic patients have a significantly decreased incretin effect. GIP (gastric inhibitory polypeptide; glucose dependent insulin releasing peptide) remains the strongest incretin factor. Its secretion depends on the absorption of nutrients. However, the correlation between the GIP response and disturbances of the entero-insular axis in some gastrointestinal diseases and, in particular, Type 2 diabetes, is poor. Furthermore, physiological concentrations of exogenous GIP do not produce fully the incretin effect and injection of GIP antibodies does not abolish the incretin effect. This suggests the existence of additional humoral incretin factors. On the other hand, GIP seems to have direct metabolic effects independent of its insulinotropic activity. The incretin effect of oral glucose is smaller if plasma levels of C-peptide rather than insulin are measured. However, decreased hepatic extraction of insulin after glucose ingestion only accounts partially for the incretin effect. GIP is unlikely to be the gut factor which regulates hepatic insulin extraction.

show abstract

Section: Direct Metabolic Effects Of Gipmentioning

confidence: 92%

New developments in the incretin concept

1985

View full text Add to dashboard Cite

show abstract

“…Receptors for GIP have been demonstrated at a number of extrapancreatic sites (8,9), suggesting a range of additional effects on nutrient metabolism. Key among these is the ability of GIP to inhibit gastric acid secretion (10), attenuate glucagon-stimulated hepatic glucose production (11), stimulate glucose uptake in muscle (12), and increase both fatty acid synthesis and lipoprotein lipase activity in adipocytes (13,14). This action profile is reminiscent, but not identical, to that displayed by glucagon-like peptide 1 (GLP-1) (15).…”

mentioning

confidence: 90%

Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes

Gault

Irwin²,

Green³

et al. 2005

Diabetes

157

108

View full text Add to dashboard Cite

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R)action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro 3 )GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro 3 )GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P < 0.05) in (Pro 3 )GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro 3 )GIP-treated group. Daily injection of (Pro 3 )GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesityrelated islet hypertrophy and ␤-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro 3 )GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes. Diabetes 54:2436 -2446, 2005 G lucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is a 42-amino acid peptide hormone secreted by enteroendocrine K-cells after nutrient absorption (1). In the pancreas, GIP stimulates glucose-dependent insulin secretion through interaction with specific heterotrimeric G-protein-coupled GIP receptors (GIP-Rs) on pancreatic ␤-cells (2). Evidence suggests that GIP also stimulates proinsulin gene transcription and translation (3) and acts as a ␤-cell growth factor (4,5) and antiapoptotic agent (6,7). Receptors for GIP have been demonstrated at a number of extrapancreatic sites (8,9), suggesting a range of additional effects on nutrient metabolism. Key among these is the ability of GIP to inhibit gastric acid secretion (10), attenuate glucagon-stimulated hepatic glucose production (11), stimulate glucose uptake in muscle (12), and increase both fatty acid synthesis and lipoprotein lipase activity in adipocytes (13,14). This action profile is reminiscent, but not identical, to that displayed by glucagon-like peptide 1 (GLP-1) (15). Together, GIP and GLP-1 constitute two major physiological incretin hormones of the enteroinsular axis (16).Much recent attention has been devoted to enhancement of incretin action using dipeptidyl peptidase (DPP) IV inhibitors or stable analogs of GLP-1 and GIP for the treatment of type 2 diabetes (17,18). Such an approach is reliant on the possibility that incretin action ...

show abstract

“…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%

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

View full text Add to dashboard Cite

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.

show abstract

Gastric inhibitory polypeptide (GIP) suppression of hepatic glucose production

Cited by 9 publications

References 0 publications

New developments in the incretin concept

New developments in the incretin concept

Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes

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

Contact Info

Product

Resources

About