Response of gastric inhibitory polypeptide to fat ingestion in normal dogs

Ohneda, Akira; Kobayashi, Takashi; Nihei, Jiro

doi:10.1016/0167-0115(84)90167-8

Cited by 10 publications

(6 citation statements)

References 15 publications

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“…There is controversy over the effects of GIP on fat metabolism, since it exhibits stimulatory actions on both lipolysis (8, 23) and lipogenesis. Triglyceride is a stronger stimulator of GIP secretion than glucose (1,2), and GIP infusion has been shown to promote clearance of chylomicron-associated TG from blood (10) and to reduce plasma TG responses to intraduodenal fat (11). GIP also stimulated adipose tissue synthesis of FA from acetate (12) as well as potentiating insulin-stimulated FA incorporation into fat (13) and enhancing LPL activity in cultured preadipocytes (14) and mature adipocytes (15).…”

Section: Discussionmentioning

confidence: 99%

“…GIP is released in response to administration of triglycerides (TG) (1,2), with long chain fatty acids (FAs) being responsible for stimulating secretion (1). In dogs, GIP has been shown to promote clearance of chylomicron-associated TG from blood (10), and in rats, it has been shown to promote infusion of GIP-lowered plasma TG responses to intraduodenal fat (11). GIP enhanced FA synthesis from acetate in adipose tissue explants (12) as well as potentiating insulin-stimulated FA incorporation into adipose tissue (13) and stimulating lipoprotein lipase (LPL) activity in cultured preadipocytes (14) and mature adipocytes (15).…”

Section: Glucose-dependent Insulinotropic Polypeptide (Gip)mentioning

confidence: 99%

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Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes

Kim

Nian

McIntosh

2007

Journal of Biological Chemistry

180

111

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Glucose-dependent insulinotropic polypeptide (GIP) has been mainly studied because of its glucose-dependent insulinotropic action and its ability to regulate ␤-cell proliferation and survival. Considerably less is known about the effects of GIP on fat metabolism, and the present study was directed at identifying the mechanisms underlying its stimulatory action on lipoprotein lipase (LPL). In differentiated 3T3-L1 adipocytes, GIP, in the presence of insulin, increased LPL activity and triglyceride accumulation through a pathway involving increased phosphorylation of protein kinase B (PKB) and reductions in phosphorylated LKB1 and AMP-activated protein kinase (AMPK). Knockdown of AMPK using RNA interference and application of the AMPK inhibitor, Compound C, supported this conclusion. In contrast, the other major incretin hormone, glucagon-like peptide-1, exhibited no significant effects on LPL activity or PKB, LKB1, or AMPK phosphorylation. Cultured subcutaneous human adipocytes showed similar responses to GIP but with greater sensitivity. Chronic elevation of circulating GIP levels in the Vancouver diabetic fatty Zucker rat in vivo resulted in increased LPL activity and elevated triglyceride accumulation in epidydimal fat tissue, combined with a modulation of PKB, LKB1, and AMPK phosphorylation similar to that observed in vitro. This appears to be the first demonstration of a GIP-stimulated signal transduction pathway involved in increasing fat storage in adipocytes. Glucose-dependent insulinotropic polypeptide (GIP)2 is a pleiotropic hormone that is released from gut endocrine cells in response to nutrient ingestion (1-3). There is strong evidence that GIP and glucagon-like peptide-1 (GLP-1) are the two most important gut-derived insulinotropic hormones, or incretins (1-4). Both incretins also exert powerful positive effects on pancreatic ␤-cell growth, development, and survival (5, 6). A number of studies have demonstrated that GIP plays an important role in the regulation of fat metabolism (7-9). GIP is released in response to administration of triglycerides (TG) (1, 2), with long chain fatty acids (FAs) being responsible for stimulating secretion (1). In dogs, GIP has been shown to promote clearance of chylomicron-associated TG from blood (10), and in rats, it has been shown to promote infusion of GIP-lowered plasma TG responses to intraduodenal fat (11). GIP enhanced FA synthesis from acetate in adipose tissue explants (12) as well as potentiating insulin-stimulated FA incorporation into adipose tissue (13) and stimulating lipoprotein lipase (LPL) activity in cultured preadipocytes (14) and mature adipocytes (15). These studies pointed to a significant role for GIP in the regulation of adipogenesis, and its physiological importance was emphasized by the demonstration by Miyawaki et al. (16) that GIP receptor knock-out mice exhibited reduced adipose tissue accretion on a high fat diet.The GIP receptor is a member of the class B seven-transmembrane G protein-coupled family to which the receptors for glucagon,...

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Section: Discussionmentioning

confidence: 99%

Section: Glucose-dependent Insulinotropic Polypeptide (Gip)mentioning

confidence: 99%

Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes

Kim

Nian

McIntosh

2007

Journal of Biological Chemistry

180

111

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“…6 In particular, 1 g per kg body weight palmitate administration in dog remarkably increases plasma GIP concentration that remains elevated for hours. 7 Free fatty acids (FFA) potentiate b-cell insulin secretion, but in the long run they allow b-cell insulin secretion impairment, ultimately inducing apoptosis. 8 We hypothesize that, similarly to what happens during a diet rich in saturated fat, intestinal chronic exposure to saturated FFA can induce apoptosis of the enterocytes and impair GIP secretion with worsening of insulin secretion and consequently hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

High saturated-fat diet induces apoptosis in rat enterocytes and blunts GIP and insulin-secretive response to oral glucose load

et al. 2008

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Lipoapoptosis has been described in many organs and tissues, but never in enterocytes. We hypothesized that a high saturatedfat diet can induce duodenal enterocyte apoptosis and impair gastric inhibitory polypeptide (GIP) secretion. Forty male Wistar rats, B4 months old, were randomized on standard laboratory or purified tripalmitin-based high-fat diet (59% calories). An oralglucose tolerance test was performed after 30 and 90 days of diet to measure plasma glucose, insulin and GIP. Duodena were processed for histology and immunohistochemistry by transferase-mediated dUTP nick end-labeling (TUNEL) method. Apoptosis was confirmed by enzyme-linked immunosorbent assay. Glycemic response was significantly higher (Po0.01 vs controls) in rats after 90 days. Insulin curve was markedly increased at 30 days, while it was blunted at 90 days. GIP area under the curve was 425.6 ± 67.6 ng ml À1 at 30 days vs 150.2 ± 33.4 ng ml À1 in controls (Po0.001) and dropped to 53.8 ± 25.8 ng ml À1 at 90 days (Po0.0001). TUNEL-positive nuclei were 66.08 ± 26.19 at 30 days 57 (34.58 ± 17 in controls, Po0.05) and 216.99 ± 129.42 nuclei per mm 3 at 90 days (38.75 ± 18.36 in controls, Po0.0001). A high saturated-fat diet stimulates GIP secretion but with time induces apoptosis of duodenal villi epithelium, showing for the first time that enterocytes are also prone to lipoapoptosis. The reduction of circulating GIP levels might contribute to hypoinsulinemia and hyperglycemia.

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“…During a meal, GIP is secreted in response to long chain fatty acids released from triglycerides (TGs) (16,17). GIP promotes the clearance of chylomicron-associated TG from blood (18) and infusion of GIP lowers rat plasma TG responses to intraduodenal fat (19). A direct adipogenic role was suggested by the demonstrations of GIP enhancement of adipose tissue fatty acid synthesis from acetate (20) and its incorporation into triglyceride (21).…”

mentioning

confidence: 99%

Resistin Is a Key Mediator of Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Lipoprotein Lipase (LPL) Activity in Adipocytes

Kim

Nian

McIntosh

2007

Journal of Biological Chemistry

107

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Response of gastric inhibitory polypeptide to fat ingestion in normal dogs

Cited by 10 publications

References 15 publications

Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes

Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes

High saturated-fat diet induces apoptosis in rat enterocytes and blunts GIP and insulin-secretive response to oral glucose load

Resistin Is a Key Mediator of Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Lipoprotein Lipase (LPL) Activity in Adipocytes

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