Session: S06-Insulin Pulsatility Matters
Room 122 (Moscone Center)
The primary function of the pancreatic beta-cell is to secrete insulin proportionally to changes in blood glucose, and its modus operandi is pulsatility. Insulin pulses are released at 5-10 minute intervals, and this interval is fairly constant in vivo and conserved across mammalian species. Pulsatile insulin release promotes optimal hepatic insulin action and signaling. Regular pulsatile insulin secretion is disrupted in patients with type 2 diabetes and their relatives, suggesting that disruptions in pulsatility may be an early warning sign of type 2 diabetes. Islets from diabetes-prone db/db mice show similar disruptions in pulsatility before becoming obese or hyperglycemic. We recently found that non-oscillatory islets isolated from db/db mice regained normal pulsatility when exposed to lower glucose conditions or to low doses of the hexokinase inhibitor D-mannoheptulose, which mildly reduces glycolytic rates. Excess glycolytic activity may thus drive beta-cells from pulsatility to continuous insulin release in early type 2 diabetes.