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

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 / min 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 microU/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.

Sympathetic Activity and Body Mass Index Contribute to Blood Pressure Levels.

“…Leptin itself has been reported to decrease insulin levels through neuropeptide-Y suppression (37). On the other hand, several investigations have demonstrated that long-term effects of insulin on leptin production can be observed both in vivo and in vitro (38,39), and also that during 2 h of euglycemic hyperinsulinemic clamp, plasma leptin concentrations remain constant in both lean and obese subjects (40). Hildebrandt and Hall et al (41) have recently reported that chronic insulin administration is unable to increase blood pressure in dogs given high doses of insulin for 28 days under conditions of euglycemia.…”

Enhanced leptin synthesis and secretion in vitro by human adipocytes from type 2 diabetic donors occurs only under hyperinsulinaemic conditions

“…23 Conversely, obesity in humans is often associated with hyperinsulinaemia and hyperleptinaemia 12,24 with serum leptin concentrations correlated with BMI. 12 Since obesity is associated with the development of metabolic conditions such as type 2 diabetes. 7,25 relationships between insulin and leptin secretion have become of great interest to researchers.…”

“…10,11 Kolaczynski et al 12 found serum leptin concentrations to be correlated with body mass index (BMI) and also to be raised in response to long-term hyperinsulinaemia in vitro. Additional rodent studies have suggested that high leptin concentrations result in decreased hypothalamic sensitivity to leptin.…”

Aspectos neuroendócrinos na síndrome dos ovários policísticos

“…A insulina pode regular a expressão do gene da leptina e seus níveis circulantes (28,29) e esta, por sua vez, pode antagonizar algumas ações da insulina através da inibição da fosforilação do receptor de insulina, tendo um papel na resistência insulínica induzida pela obesidade e observada nos pacientes com DM 2 (30). Por outro lado, embora a secreção de leptina não seja modificada por um estado de hiperinsulinemia aguda, a hiperinsulinemia sustentada ou resistência à insulina promove aumento dos níveis de leptina sérica (31)(32)(33).…”