Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency.
Serum leptin levels were unchanged by hyperinsulinemia for 3 h during the clamp prior to the fast, while hyperinsulinemia for 3 h after 6 days of fasting increased serum leptin by 25% (P < 0.01).
To investigate the role of chronic hyperinsulinemia in the regulation of plasma leptin concentrations, we studied 13 patients with surgically confirmed insulinoma before and after tumor removal, along with 15 healthy control subjects matched for sex, age, and BMI.
We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes.
Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted food intake and body weight gain response to fasting without affecting basal ARC NPY gene expression.
To that end, we conducted a double-blind, placebo-controlled study of the effects of metformin on body mass index (BMI), serum leptin, glucose tolerance, and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.
Leptin resistance in obese individuals is frequently associated with insulin resistance and pronounced hyperinsulinaemia indicating a negative crosstalk of the insulin and leptin signalling chain.
Women with polycystic ovaries on ultrasound have increased insulin sensitivity and possible leptin resistance, which could predispose to future weight gain.
This study demonstrates that targeted POMC gene delivery in the hypothalamus suppresses food intake and weight gain and reduces visceral adiposity and hyperinsulinemia in leptin-resistant obese Zucker rats.
Further, we document here the efficacy of leptin replenishment in vivo, especially by supplying it to the hypothalamus with the aid of gene therapy, in preventing the antecedent pathophysiological sequalae--hyperinsulinemia, insulin resistance and hyperglycemia--in various animal models and clinical paradigms of diabetes type 1 and 2 with or without attendant obesity.
In first-degree relatives normal glucose tolerant women, fasting hyperinsulinemia, independently of the presence of metabolic syndrome, is associated with elevated IL-6 and leptin levels, suggesting an increased cardiovascular risk.
Further, similar hypothalamic leptin transgene expression abrogated chronic hyperglycemia and hyperinsulinemia, the predisposing risk factors of the age and environmentally acquired diabetes type 2, and instituted euglycemia by independently activating relays that stimulate glucose metabolism and repress hyperinsulinemia and improve insulin sensitivity in the periphery.
These results identify a novel molecular pathway by which leptin confers inhibitory action on insulin secretion, and impaired PP-1 inhibition by leptin may be involved in dysfunction of the adipoinsular axis during the development of hyperinsulinemia and type 2 diabetes mellitus.
Analyses of metabolic parameters in maternal venous and umbilical venous plasma revealed significantly increased insulin and leptin as well as slightly increased glucose and TNF-α values in the obese and obese-GDM groups.