The Effect of Obesity on the α-Cell Response to Hyperglycemia in the Presence of Amino Acids.

Mohan, Sneha; Boscolo, Federica; Christie, Hannah E; Egan, Aoife M; Bailey, Kent R; Jensen, Michael D; Nair, K Sree; Dalla Man, Chiara et al. · Diabetes · 2026

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Abstract

The aim of this study was to understand the pathogenesis of α-cell dysfunction in prediabetes. The primary hypothesis was that α-cell responsivity to glucose (reduction of the glucagon secretion rate by 50%) is impaired by amino acid (AA) infusion. A secondary hypothesis was that this abnormal response is exacerbated by hepatic steatosis. AA infusion impaired α-cell suppression in response to rising glucose in participants with obesity, but not in lean participants, despite a normal response to glucose alone. This abnormal response was unaffected by the presence or absence of hepatic steatosis. It seems likely that an abnormal α-cell response to AAs precedes an abnormal response to glucose alone.