Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. 2; pp. 131 - 145
• Main Authors: Taddeo, Evan P., Alsabeeh, Nour, Baghdasarian, Siyouneh, Wikstrom, Jakob D., Ritou, Eleni, Sereda, Samuel, Erion, Karel, Li, Jin, Stiles, Linsey, Abdulla, Muhamad, Swanson, Zachary, Wilhelm, Joshua J., Bellin, Melena D., Kibbey, Richard G., Liesa, Marc, Shirihai, Orian S.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.02.2020
• Subjects: Animals; Beta cells; Blood Glucose; Cyclophilins - genetics; Cyclophilins - metabolism; Diabetes; Diabetes mellitus (non-insulin dependent); Diet, High-Fat; Fasting; Fatty acids; Fatty Acids, Nonesterified - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glucose; Humans; Hyperinsulinemia; Insulin; Insulin resistance; Insulin secretion; Insulin Secretion - drug effects; Islets of Langerhans - metabolism; Membrane permeability; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; Mitochondrial permeability transition pore; Oleic Acid - chemistry; Oleic Acid - pharmacology; Oxygen Consumption; Palmitic Acid - chemistry; Palmitic Acid - pharmacology; Pancreas; Peptidyl-Prolyl Isomerase F - metabolism; Protons; Secretion

Fasting hyperinsulinemia precedes the development of type 2 diabetes. However, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence of the progressive increase in fasting glycemia induced by insulin resistance in the prediabetic state. Herei...