Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Endogenous glucagon-like peptide-1 mediates the lowering of glycaemia during small intestinal glucose infusion by bile acids in type 2 diabetes (#136)

Tongzhi Wu 1 2 , Michael Horowitz 1 2 , Karen Jones 1 2 , Chris Rayner 1 2
  1. Discipline of Medicine, The University of Adelaide, Adelaide, SA, Australia
  2. Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia

Background: Bile acids are recognised to play an important role in glucose homeostasis. We have reported that small intestinal administration of taurocholic acid (TCA) reduces the glycaemic response to intrajejunal (IJ) glucose infusion markedly in health, associated with stimulation of glucagon-like peptide-1 (GLP-1). Here, we evaluated the effects of TCA, with or without the GLP-1 receptor antagonist, exendin(9-39), during an IJ glucose infusion in type 2 diabetes (T2DM).

Methods: 10 T2DM patients were each studied on four days, when an IJ catheter was positioned and a balloon inflated to exclude endogenous bile. An intravenous exendin(9-39) (600pmol/kg/min) or saline was commenced and maintained during t=-60-120min. TCA (2g), or saline, was given via IJ infusion during t=-30-0min, followed by 2g TCA or saline, together with 60g glucose, during t=0-120min. Blood glucose and plasma hormones were measured. The insulin secretion rate (ISR)/glucose ratio was calculated. Incremental areas under the curves during t=-60-120min were compared using repeated measures ANOVA, with TCA and exendin(9-39) as factors.

Results: TCA reduced blood glucose (P=0.022, treatment effect), and increased plasma insulin (P=0.007) and the ISR/glucose ratio (P=0.022), without affecting plasma glucagon. Exendin(9-39) augmented blood glucose (P=0.003) and plasma glucagon (P=0.011), decreased plasma insulin (P=0.008) and the ISR/glucose ratio (P<0.001). Without exendin(9-39), blood glucose was lower (P = 0.010), and plasma insulin (P = 0.025) and the ISR/glucose ratio (P=0.039) were greater, with TCA vs. control, without any difference in glucagon. With exendin(9-39), insulin was greater with TCA vs. control (P=0.020), without any difference in blood glucose, the ISR/glucose ratio, or glucagon.

Conclusion: In T2DM, small intestinal TCA reduces the glycaemic response to IJ glucose, associated with increased insulin secretion, and these effects are attenuated by exendin(9-39). These observations support the concept of a “bile acid-GLP-1” axis in the regulation of postprandial glycaemia in T2DM.