Acute and Chronic Effect of Insulin on Leptin Production in Humans: Studies In Vivo and In Vitro

TLDR

The study examined how insulin affects OB gene expression and leptin production in humans under euglycemic and hyperglycemic conditions, both in vitro and in vivo. The authors employed a euglycemic clamp with escalating insulin doses in lean, obese, and NIDDM participants, a 64‑to‑72‑hour hyperglycemic clamp in lean subjects, and a 96‑hour adipocyte culture with or without insulin. Short‑term hyperinsulinemia did not alter circulating leptin, but prolonged hyperglycemia and long‑term insulin exposure increased leptin and OB gene expression, indicating insulin indirectly stimulates leptin production over time.

Abstract

This study was undertaken to investigate the changes in obesity (OB) gene expression and production of leptin in response to insulin in vitro and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU · m−2 · min−1 carried out for up to 5 h performed in 16 normal lean individuals, 30 obese individuals, and 31 patients with NIDDM; 2) 64-to 72-h hyperglycemic (glucose 12.6 mmol/l) clamp performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the range of 80 to > 10,000 μU/ml had no effect on circulating levels of leptin. During the prolonged hyperglycemic clamp, a rise in leptin was observed during the last 24 h of the study (P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; however, a long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro. These data suggest that insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.