Give the Receptor a Brake: Slowing Gastric Emptying by GLP-1

  1. David D’Alessio1,2
  1. 1Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, OH
  2. 2Cincinnati Veterans Affairs Medical Center, Cincinnati, OH
  1. Corresponding author: Jenny Tong, jenny.tong{at}

The conventional view of endocrinologists is that glucose regulation after a meal depends on the interplay of insulin and glucagon secretion, hepatic glucose production, and glucose disposal. However, in recent years the role of gastric motility and its effect on glucose appearance from the gut have been revived as a determinant of glucose tolerance (1,2). This is due in great part to the availability of diabetes therapeutics that act, in part, by delaying gastric emptying (GE). Yet it is important to note that much of the variance in oral glucose tolerance is accounted for by differences in GE rate, an observation made over two decades ago (1). Even a minor perturbation in GE carries a substantial impact on postprandial glycemia in healthy individuals (1) and those with diabetes (3), such that more rapid GE results in a greater initial glycemic response and slower gastric delivery of meal contents to the intestine leads to smaller glucose excursion (4).

Glucagon-like peptide 1 (GLP-1) normalizes glycemia by promoting glucose-dependent insulin secretion and inhibiting glucagon secretion in the fasting state (5). A deceleration of GE is also characteristic of GLP-1 action and occurs both in patients with type 2 diabetes (T2D) and healthy individuals (68). In fact, glucose lowering by GLP-1 was significantly attenuated when the actions on GE were overridden by treatment with erythromycin (9). This has led to questions as to whether islet or gastrointestinal effects of GLP-1 predominate in its effects on glycemia (10). Long-acting GLP-1 receptor (GLP-1R) agonists, recently developed and now commonly used in the treatment of T2D, stimulate insulin secretion and reduce GE (5), but the relative impact of these two physiologic actions on acute and chronic control of blood glucose is not clear.

Recent studies have raised the …

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