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Insulin sensitivity depends on the route of glucose administration – published online 08/05/2020

Graphical abstract for Mingrone

Geltrude Mingrone, Simona Panunzi, Andrea De Gaetano, Sofie Ahlin, Valerio Spuntarelli, Isabel Bondia-Pons, Chiara Barbieri, Esmeralda Capristo, Amalia Gastaldelli, John J Nolan

Bariatric surgery results in a rapid improvement in insulin resistance long before weight loss, focusing attention on the role of the small intestine in insulin resistance. In this issue, Mingrone et al (https://doi.org/10.1007/s00125-020-05157-w) compared glucose metabolism in obese participants who were administered oral glucose and, after 7–10 days, i.v. glucose (plasma glucose during i.v. administration was matched to plasma glucose during oral challenge). They also analysed the differences in insulin effect on proteolysis, ketogenesis and lipolysis. The authors found that the oral route led to increased insulin secretion and a complementary 40% reduction in glucose clearance, as compared with the i.v. route. The efficacy of insulin to reduce lipolysis and proteolysis also decreased after oral glucose administration. The authors suggest that an unknown mechanism, triggered by the presence of glucose in the intestinal lumen, counterbalances the effect of incretins (gut hormones that stimulate insulin secretion) by limiting the effect of insulin that has been released in response to glucose. They conclude that these findings indicate that insulin sensitivity depends on the route of glucose administration and that (as yet unknown) intestinal factors are crucial to these underlying metabolic processes.

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