2211-LB: Oxygen Consumption in Human Islets Is Increased in Type 2 Diabetes

Le résumé fourni par la source

Introduction and Objective: Metabolic aberrations in type 2 diabetes (T2D) include pancreatic mitochondrial dysfunction, thus, we investigated non-glucose and glucose-stimulated oxygen consumption (OC) in human islets from donors with T2D. Methods: Data were from the Human Pancreas Analysis Program (T2D n=19, healthy n=43). Area under the curve OC was generated across 30 min perifusion phases: no substrate/baseline, 4 mM amino acid mixture (AAM), AAM+ 3mM glucose, AAM + 16.7mM glucose, AAM + 16.7 glucose + FCCP. Insulin and glucagon secretion measurements were collected during additional perifusion experiments of similar phases (IBMX instead of FCCP). We compared T2D and controls using t-tests and multivariate linear regression. Results: T2D donors were older and had greater islet OC across all phases vs. healthy islets (Table 1). Insulin secretion was significantly lower in T2D (vs. healthy) islets except during AAM+3mM glucose. In contrast, T2D glucagon secretion was significantly lower during AAM+ 3 mM glucose. The interaction of OC x glucagon was associated with insulin secretion during AAM (interaction β= 0.0005, p=0.014), adj for age and baseline OC. Similarly, OC x insulin was associated with glucagon secretion in AAM (adj β= 1315, p=0.0036) and glucose 3mM (adj β=768, p=0.0035). Conclusion: Islets from T2D had higher OC but lower insulin and glucagon secretion. The decoupling of respiration and hormone secretion may impact interdependent functional control across alpha and beta cells. Disclosure L.Staimez: n/a. C.Huang: None. M.K.Bhasin: None. K.Narayan: None. P.Vellanki: n/a. D.A.Reiter: None. Funding National Institutes of Health (DK112217, U01-DK123594, UC4-DK112232, U01-DK123716, and K01DK133669 for L.S.); Human Pancreas Analysis Program (RRID:SCR_014393)

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.