Priming effect of glucagon-like peptide-1 (7–36) amide, glucose-dependent insulinotropic polypeptide and cholecystokinin-8 at the isolated perfused rat pancreas

Fehmann, Hans-Christoph; Göke, Rüdiger; Göke, Burkhard; Bächle, Rolf; Wagner, Birte; Arnold, R.

doi:10.1016/0167-4889(91)90200-h

Cited by 40 publications

(23 citation statements)

References 46 publications

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“…This is in agreement with other studies where no, or only a small, increase in plasma insulin concentrations was seen at low plasma glucose concentrations and plasma GLP-1 concentrations around 16 pmol·l -1 [49,53]. In vitro studies have shown that GLP-1 has a priming effect on glucosestimulated insulin secretion [50,54] but in vivo pretreatment with GLP-1 for 60 min did not alter the subsequent beta-cell response to glucose [49]. Therefore, the increase in plasma GLP-1 concentrations during the glucose infusion is probably more physiologically relevant to affect insulin secretion than the high plasma GLP-1 concentrations before the clamp.…”

Section: Discussionsupporting

confidence: 92%

Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

et al. 2002

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Aims/hypothesis. Fatty acids affect insulin secretion in vivo, but little is known about the effects of specific fatty acids. Our aim was to investigate differential effects of acutely increased plasma monounsaturated, polyunsaturated and saturated fatty acids on glucosestimulated insulin secretion in healthy humans. Methods. A new experimental protocol was used to increase plasma monounsaturated (MUFA test), polyunsaturated (PUFA test) or saturated (SFA test) nonesterified fatty acids for 2 h by repeated oral fat feeding and continuous intravenous heparin infusion. This was followed by a hyperglycaemic clamp (10 mmol/l) to test insulin secretion in response to a prior plasma NEFA increase. Results. Total plasma NEFA concentrations were increased during the fat tests compared to the control visit (1.7-fold increase for MUFA and SFA tests and 1.4-fold increase for PUFA test; p<0.001). Exaggerated responses in plasma insulin, C-peptide and proinsulin concentrations were seen during the hyperglycaemic clamp after increasing plasma NEFA concentrations compared with the control (p<0.01). The effects were greatest for the MUFA test followed by the PUFA test and SFA test (p<0.01). Plasma GLP-1 concentrations increased during fat feeding, with a higher response during the MUFA test compared to PUFA and SFA tests (p<0.01). Conclusion/interpretation. Increasing plasma NEFA concentrations by oral fat feeding with heparin infusion augments glucose-stimulated insulin secretion with the greatest effect for monounsaturated fatty acids and the lowest effect for saturated fatty acids. Monounsaturated fatty acids also increase GLP-1 more than saturated fatty acids. Therefore, the exaggerated insulin concentrations could be due to both NEFA and GLP-1. [Diabetologia (2002[Diabetologia ( ) 45:1533[Diabetologia ( -1541 Keywords Monounsaturated fatty acids, polyunsaturated fatty acids, saturated fatty acids, insulin secretion, GLP-1. High fat diets lead to obesity, which in turn is one of the main causes of the development of Type II (noninsulin-dependent) diabetes mellitus. Both obesity and Type II diabetes are characterized by increased plasma non-esterified fatty acid concentrations [1] and raised fasting plasma NEFA concentrations are a risk marker for the development of Type II diabetes in Caucasian subjects [2] and in Pima Indians [3]. Increased plasma NEFA concentrations can have adverse effects on various tissues. Excess plasma NEFA concentrations can lead to a reduced skeletal muscle glucose uptake and oxidation [4,5,6], increased hepatic glucose output [7] and a decrease in hepatic insulin clearance [8,9]. These mechanisms could lead to glucose intolerance and insulin resistance leading to Type II diabetes.Inappropriately high concentrations of plasma NEFA have also been shown to alter glucose-stimulat-

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Section: Discussionsupporting

confidence: 92%

Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

et al. 2002

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“…The anti-insulin monoclonal antibody was from Sigma. The anti-IGF-1 receptor and anti-insulin receptor antibodies were from Santa Cruz Biotechnology; both antibodies were raised against the N-terminal unique sequences (amino acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] of the corresponding receptor. IGF-1 was from Becton Dickinson or GIBCO͞BRL.…”

Section: Methodsmentioning

confidence: 99%

“…Many insulin secretagogues that utilize cAMP as a second messenger will potentiate glucose-stimulated insulin secretion (1,8,9), and agents that elevate cAMP, such as nonspecific phosphodiesterase (PDE) inhibitors (e.g., isobutylmethylxanthine and theophylline), are potent insulin secretagogues (10)(11)(12). Several recent studies have suggested the presence of both PDE3 and PDE4 activities within pancreatic islets (for a review about various types of PDEs, see ref.…”

mentioning

confidence: 99%

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

Zhao

Teague

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

138

115

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Both insulin and insulin-like growth factor 1 (IGF-1) are known to reduce glucose-dependent insulin secretion from the ␤ cells of pancreatic islets. In this paper we show that the mechanism by which IGF-1 mediates this effect is in large part through activation of a specific cyclic nucleotide phosphodiesterase, phosphodiesterase 3B (PDE3B). More specifically, in both isolated pancreatic islets and insulin-secreting HIT-T15 cells, IGF-1 inhibits insulin secretion that has been increased by glucose and glucagonlike peptide 1 (GLP-1). Moreover, IGF-1 decreases cAMP levels in parallel to the reduction of insulin secretion. Insulin secretion stimulated by cAMP analogs that activate protein kinase A and also are substrates for PDE3B is also inhibited by IGF-1. However, IGF-1 does not inhibit insulin secretion stimulated by nonhydrolyzable cAMP analogs. In addition, selective inhibitors of PDE3B completely block the ability of IGF-1 to inhibit insulin secretion. Finally, PDE3B activity measured in vitro after immunoprecipitation from cells treated with IGF-1 is higher than the activity from control cells. Taken together with the fact that pancreatic ␤ cells express little or no insulin receptor but large amounts of IGF-1 receptor, these data strongly suggest a new regulatory feedback loop model for the control of insulin secretion. In this model, increased insulin secretion in vivo will stimulate IGF-1 synthesis by the liver, and the secreted IGF-1 in turn feedback inhibits insulin secretion from the ␤ cells through an IGF-1 receptormediated pathway. This pathway is likely to be particularly important when levels of both glucose and secretagogues such as GLP-1 are elevated.

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“…A short lasting preinfusion of GLP-l(7-36) amide, GIP, and CCK induced an augmented insulin secretion in response to subsequent glucose stimulation [58].…”

Section: ( 4 ) Interaction Of Glp-1(7-36) Amide With Other Hormonesmentioning

confidence: 99%