Insulin-dependent inhibition of hepatic glycogenolysis by gastric inhibitory polypeptide (GIP) in perfused rat liver

Hartmann, Heinz; Ebert, R.; Creutzfeldt, W.

doi:10.1007/bf00456120

Cited by 35 publications

(17 citation statements)

References 17 publications

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“…1). This observation is consistent with the reports of increased glycogenolysis in response to decreased insulin concentration (19,44). Enhanced insulin sensitivity can potentially stimulate glycogen synthesis during glucose availability, resulting in increased glycogen stores.…”

Section: Discussionsupporting

confidence: 92%

Effect of ghrelin on glucose regulation in mice

Chacko

Haymond

Sun

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Improvement of glucose metabolism after bariatric surgery appears to be from the composite effect of the alterations in multiple circulating gut hormone concentrations. However, their individual effect on glucose metabolism during different conditions is not clear. The objective of this study was to determine whether ghrelin has an impact on glycogenolysis, gluconeogenesis, and insulin sensitivity (using a mice model). Rate of appearance of glucose, glycogenolysis, and gluconeogenesis were measured in wild-type (WT), ghrelin knockout (ghrelin Ϫ/Ϫ ), and growth hormone secretagogue receptor knockout (Ghsr Ϫ/Ϫ ) mice in the postabsorptive state. The physiological nature of the fasting condition was ascertained by a short-term fast commenced immediately at the end of the dark cycle. Concentrations of glucose and insulin were measured, and insulin resistance and hepatic insulin sensitivity were calculated. Glucose concentrations were not different among the groups during the food-deprived period. However, plasma insulin concentrations were lower in the ghrelin Ϫ/Ϫ and Ghsr Ϫ/Ϫ than WT mice. The rates of gluconeogenesis, glycogenolysis, and indexes of insulin sensitivity were higher in the ghrelin Ϫ/Ϫ and Ghsr Ϫ/Ϫ than WT mice during the postabsorptive state. Insulin receptor substrate 1 and glucose transporter 2 gene expressions in hepatic tissues of the ghrelin Ϫ/Ϫ and Ghsr Ϫ/Ϫ were higher compared with that in WT mice. This study demonstrates that gluconeogenesis and glycogenolysis are increased and insulin sensitivity is improved by the ablation of the ghrelin or growth hormone secretagogue receptor in mice.ghrelin; growth hormone secretagogue receptor; gluconeogenesis; bariatric surgery; insulin sensitivity THE IMPROVEMENT IN INSULIN SENSITIVITY and in many cases reversal of type 2 diabetes after bariatric surgery procedures before any weight loss occurs are well established (6,14,16,30,46,60). Improved glycemic control achieved immediately after surgery but before weight loss suggests a hormonal mechanism (10, 30). After bariatric surgery, fasting insulin concentrations dropped dramatically during the first week and persisted up to two years (30). The plasma ghrelin concentrations were decreased by ϳ70% following gastric bypass surgery compared with matched obese and normal-weight controls (10). Although beneficial effect of bariatric surgery on glucose metabolism has been associated with changes in several circulating gut hormone concentrations (26,40,61), their individual effect during different conditions remains to be elucidated. The relationship between the improvement of glucose metabolism and reduced ghrelin concentration as well as the effect of ghrelin on the constituents of glucose production remain unclear.The stomach is the major source of circulating ghrelin. Furthermore, ghrelin-containing cells are particularly abundant in the fundus region of the stomach (1,20,53,64). Sleeve gastrectomy, which involves the complete resection of the gastric fundus, resulted in better glycemic control compared wit...

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Section: Discussionsupporting

confidence: 92%

Effect of ghrelin on glucose regulation in mice

Chacko

Haymond

Sun

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Based on these results, it seems that these novel N-terminal Tyr 1 -modified analogues of GIP enhance insulin secretion in vivo and improve glycaemic responses in Type II diabetes by conferring DPP IV resistance as well as increased potency at the GIP receptor. Moreover GIP has been proposed to exert various extrapancreatic effects, which could contribute to anthyperglycaemic activity in vivo including stimulation of peripheral glucose uptake [16,53,54,55].…”

Section: Discussionmentioning

confidence: 99%

Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP

et al. 2002

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Aims/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3′5′ monophosphate (cAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice. Results. GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t 1/2 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p<0.001) at stimulating cAMP production (EC 50 values 1.9 and 2.7 nmol/l, respectively), almost a tenfold increase compared to native GIP (18.2 nmol/l). Both Ac-GIP and pGlu-GIP (10 -13 -10 -8 mmol/l) were more potent at stimulating insulin release compared to the native GIP (p<0.001), with 1.3-fold and 1.2-fold increases observed at 10 -8 mol/l, respectively. Administration of GIP analogues (25 nmol/kg body weight, i.p.) together with glucose (18 mmol/kg) in (ob/ob) mice lowered (p<0.001) individual glucose values at 60 min together with the areas under the curve for glucose compared to native GIP. This antihyperglycaemic effect was coupled to a raised (p<0.001) and more prolonged insulin response after administration of Ac-GIP and pGlu-GIP (AUC, 644±54 and 576±51 ng·ml -1 ·min, respectively) compared with native GIP (AUC, 257±29 ng·ml -1 ·min). Conclusion/interpretation. Ac-GIP and pGlu-GIP, show resistance to plasma dipeptidylpeptidase IV degradation, resulting in enhanced biological activity and improved antidiabetic potential in vivo, raising the possibility of their use in therapy of Type II (non-insulin-dependent) diabetes mellitus. [Diabetologia (2002[Diabetologia ( ) 45:1281[Diabetologia ( -1291 Keywords GIP analogues, antihyperglycaemic effects, insulin secretion, DPP IV stability, BRIN-BD11 cells, obese hyperglycaemic (ob/ob) mice. Corresponding author: Dr. F. P. M. O'Harte, School of Biomedical Sciences, University of Ulster, Coleraine, N. Ireland, UK, BT52 1SA, E-mail: fpm.oharte@ulst.ac.uk Abbreviations: cAMP, Cyclic adenosine 3′ 5′ monophosphate; DPP IV, Dipeptidylpeptidase IV; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide-1(7-36)amide; TFA, trifluoroacetic acid; ESI-MS, electrospray ionisation mass spectrometry; pGlu, N-pyroglutamyl; Ac, N-acetyl; Fmoc, 9-fluorenylmethoxycarbonyl; CHL, Chinese hamster lung fibroblast; DPA, diprotin A; FSK, forskolin; IBMX, isobutylmethylxanthine Diabetologia (2002) 45:1281-1291 DOI 10.1007 Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP Type II (non-insulin-dependent) diabetes me...

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“…In liver, GIP has been shown to enhance insulin-dependent inhibition of glycogenolysis (Elahi et al 1986). GIP also reduces both glucagon-stimulated lipolysis in adipose tissue and hepatic glucose production (Hartmann et al 1986). Finally, other findings in our laboratory indicate that GIP has a potent effect on glucose uptake and metabolism in isolated mouse diaphragm muscle (O'Harte et al 1998c).…”

Section: Discussionmentioning

confidence: 99%

Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide

O’Harte

Mooney²,

Kelly³

et al. 2000

Journal of Endocrinology

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Gastric inhibitory polypeptide (GIP) is an important insulin-releasing hormone of the enteroinsular axis which is rapidly inactivated by the exopeptidase dipeptidyl peptidase (DPP) IV. The present study has examined the ability of Tyr 1 -glucitol GIP to be protected from plasma degradation and to enhance insulin-releasing and antihyperglycaemic activity in 20-to 25-week-old obese diabetic ob/ob mice. Degradation of GIP by incubation at 37 C with obese mouse plasma was clearly evident after 3 h (35% degraded). After 6 h, more than 61% of GIP was converted to GIP(3-42) whereas N-terminally modified Tyr 1 -glucitol GIP was resistant to degradation in plasma (>99% intact after 6 h). The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A. Effects of GIP and Tyr -glucitol GIP also enhanced the glucose-lowering ability of 50 units/kg insulin (218·4 30·2 vs insulin alone 133·9 16·2 mmol/l.min; P<0·05). These data demonstrate that Tyr 1 -glucitol GIP displays resistance to plasma DPP IV degradation in a commonly used animal model of type 2 diabetes, resulting in enhanced antihyperglycaemic activity and insulin-releasing action in vivo.

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Insulin-dependent inhibition of hepatic glycogenolysis by gastric inhibitory polypeptide (GIP) in perfused rat liver

Cited by 35 publications

References 17 publications

Effect of ghrelin on glucose regulation in mice

Effect of ghrelin on glucose regulation in mice

Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP

Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide

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