Glucagon secretion in relation to insulin sensitivity in healthy subjects

Abstract

Aims/hypothesis: The study evaluated whether glucagon secretion is regulated by changes in insulin sensitivity under normal conditions. Materials and methods: A total of 155 healthy women with NGT (aged 53-70 years) underwent a glucose-dependent arginine-stimulation test for evaluation of glucagon secretion. Arginine (5 g) was injected i.v. under fasting conditions (plasma glucose 4.8±0.1 mmol/l) and after raising blood glucose concentrations to 14.8±0.1 and 29.8±0.2 mmol/l. The acute glucagon response (AGR) to arginine during the three glucose levels (AGR 1 , AGR 2 , AGR 3 ) was estimated, as was the suppression of baseline glucagon by the increased glucose. All women also underwent a 2-h euglycaemic-hyperinsulinaemic clamp study for estimation of insulin sensitivity. Results: Insulin sensitivity was normally distributed, with a mean of 73.2±29.3 (SD) nmol glucose kg −1 min −1 /pmol insulin l −1 . When relating the variables obtained from the arginine test to insulin sensitivity, insulin resistance was associated with increased AGR and with increased suppression of glucagon levels by glucose. For example, the regression between insulin sensitivity and AGR 2 was r=−0.38 (p<0.001) and between insulin sensitivity and suppression of glucagon levels by 14.8 mmol/l glucose r=0.36 (p<0.001). Insulin sensitivity also correlated negatively with insulin secretion; multivariate analysis revealed that changes in insulin sensitivity and insulin secretion were independently related to changes in glucagon secretion. Conclusions/ interpretation: The body adapts to insulin resistance by increasing the glucagon response to arginine and by increasing the suppression of glucagon levels by glucose. Hence, not only the islet beta cells but also the alpha cells seem to undergo compensatory changes during the development of insulin resistance.

Association of insulin resistance and GLP-2 secretion in obesity: a pilot study

“…GLP-2 directly stimulates glucagon secretion and counteracts the glucagonostatic action of GLP-1 in healthy subjects (9), and in type 1 and type 2 diabetic subjects (3,16). Glucagon is counter-regulatory to insulin action, increasing glucose output and inhibiting glucose uptake in the liver, and has been linked to IR in obese subjects with normal or impaired glucose tolerance (17,18).…”

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

“…Hypothesis has been advanced that GLP2-increased secretion could be the cause of insulin resistance as GLP2 increases absorption of nutrients, especially fatty acids, a key factor for insulin resistance (Delarue & Magnan 2007) or for its glucagonotrophic action in healthy or diabetic subjects (Christensen et al 2010, Lund et al 2011. Glucagon is counter-regulatory to insulin action, increasing glucose output and inhibiting glucose uptake in the liver, and it has been linked to insulin resistance in obese subjects with normal or impaired glucose tolerance (Ahrén 2006, Weiss et al 2011. However, this appears unlikely because bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB) (Saeidi et al 2013), which is the most effective therapy for obesity and T2D (Carlsson et al 2012, Cummings 2012, increases blood GLP2 (by 200%) at postprandial status (le Roux et al 2010).…”

Pancreatogenic Diabetes after Pancreatic Resection

“…By comparison, the decrease in glucagon from fasting promotes a hypoglycemic state when patients have been administered only a slight excess of insulin. Under physiological conditions, glucagon secretion decreases following a glucose load, thereby avoiding hyperglycemia [43,44]. In type 2 diabetes, however, the suppression of glucagon induced by glucose is frequently decreased [44] and postprandial hyperglucagonemia is associated with hyperglycemia because of increased hepatic glucose production.…”