Leptin is an adipocyte-derived
hormone that primarily acts in the hypothalamus and plays a key role in the regulation of food intake,
body weight, energy expenditure and neuroendocrine function.
Leptin has direct peripheral effects on several tissues, and it may be independently involved in insulin secretion and action besides its effects on
body weight regulation. Basal plasma
leptin and
insulin concentrations correlate with each other.
Insulin and
glucose appear to increase
leptin secretion. In turn,
leptin increases peripheral
insulin sensitivity while decreasing insulin secretion from pancreatic beta cells.
Leptin increases skeletal muscle
glucose uptake and oxidation, and suppresses hepatic
glucose output. Effects of
leptin on lipid metabolism might reduce lipotoxicity and therefore contribute to the improvement of hepatic, skeletal and whole body
insulin sensitivity.
Leptin is the first
adipokine used in the treatment of hypoleptinemic clinical disorders. Although
leptin therapy has limited success in common
obesity, it has impressive effects in congenital
leptin deficiency,
lipoatrophic diabetes and syndromes of severe
insulin resistance.
Leptin has been reported to ameliorate
hyperinsulinemia and diabetes in the clinical setting of congenital
leptin deficiency. It also improves
hyperglycemia,
insulin resistance,
hyperinsulinemia,
dyslipidemia and hepatic steatosis in
lipoatrophic diabetes. These promising results warrant clinical trials to test the hypothesis that
leptin alone or with classical
antidiabetic agents may potentially be beneficial in the treatment of hypoleptinemic non-obese individuals with
glucose intolerance and diabetes. This review summarizes the clinical applications of
leptin, particularly emphasizing the effects of
leptin on
glucose homeostasis.