Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7, 51
eCollection

The Role of Leptin in the Control of Insulin-Glucose Axis

Affiliations

The Role of Leptin in the Control of Insulin-Glucose Axis

Marie Amitani et al. Front Neurosci.

Abstract

Obesity and diabetes mellitus are great public health concerns throughout the world because of their increasing incidence and prevalence. Leptin, the adipocyte hormone, is well known for its role in the regulation of food intake and energy expenditure. In addition to the regulation of appetite and satiety that recently has attracted much attentions, insight has also been gained into the critical role of leptin in the control of the insulin-glucose axis, peripheral glucose and insulin responsiveness. Since the discovery of leptin, leptin has been taken for its therapeutic potential to obesity and diabetes. Recently, the therapeutic effects of central leptin gene therapy have been reported in insulin-deficient diabetes in obesity animal models such as ob/ob mise, diet-induced obese mice, and insulin-deficient type 1 diabetes mice, and also in patients with inactivating mutations in the leptin gene. Herein, we review the role of leptin in regulating feeding behavior and glucose metabolism and also the therapeutic potential of leptin in obesity and diabetes mellitus.

Keywords: adipo-insulin axis; food intake; leptin; leptin gene therapy.

Figures

Figure 1
Figure 1
Leptin binds to the leptin receptor (LepRb) and activates the receptor-associated kinase JAK2 via transphosphorylation and phosphorylates three tyrosine residues (Y985, Y1077, and Y1138). Leptin-induced mRNA expression of JAK-STAT is inhibited by SOCS3. Insulin and leptin regulate the expression of AgRP and POMC via Foxo1 and signal transducer and activator of transcription factor Stat3. Sirt1 suppresses the Foxo1-dependent expression of the orexigenic neuropeptide AgRP. AgRP, agouti-related protein; FOXO1, Forkhead box O1; IRS, insulin receptor substrate; PI3K, phosphatidylinositol 3 kinase; PIP3, phosphatidylinositol 3, 4, 5-triphosphate.
Figure 2
Figure 2
Circulating leptin is correlated with the degree of adiposity and is transported across the blood-brain barrier (BBB). In hypothalamus, leptin activates POMC and CART neurons, and inhibit NPY and AgRP neurons, lead to anorexia. Leptin has effect to feeding behavior, appetite, insulin-glucose axis, and cognitive function. (A) In leptin sensitive individuals, leptin inhibits insulin biosynthesis and secretion from pancreatic β-cells. By contrast, insulin stimulates leptin secretion from adipose tissue. Leptin stimulates hepatic gluconeogenesis and hepatic insulin sensitivity via the hepatic branch of the vagus nerve. Additionally, leptin increases glucose uptake in the skeletal muscle, heart, and brown adipose tissue (BAT) via the sympathetic nervous system. (B) In leptin resistant over-weight individuals, the permeability of the BBB to leptin is decreased in high-fat diet-induced obesity despite the increase in plasma leptin levels. This impaired transport of leptin across the BBB is one of the causes of leptin resistance. Insufficiency of leptin signaling in the hypothalamus (induced by hyperleptinemia in obese subjects), causes hyperglycemia and hyperinsulinemia, which lead to diabetes mellitus. AgRP, agouti-related protein; ARC, arcuate nucleus; CART, cocaine-and-amphetamine responsive transcript; LHA, lateral hypothalamic area; NPY, neuropeptide Y; POMC, proopiomelanocortin; BBB, blood-brain barrier.

Similar articles

See all similar articles

Cited by 32 PubMed Central articles

See all "Cited by" articles

References

    1. Ahima R. S., Prabakaran D., Flier J. S. (1998). Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function. J. Clin. Invest. 101, 1020–1027 10.1172/JCI1176 - DOI - PMC - PubMed
    1. Ahima R. S., Saper C. B., Flier J. S., Elmquist J. K. (2000). Leptin regulation of neuroendocrine systems. Front. Neuroendocrinol. 21, 263–307 10.1006/frne.2000.0197 - DOI - PubMed
    1. Akiyama T., Tachibana I., Shirohara H., Watanabe N., Otsuki M. (1996). High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat. Diabetes Res. Clin. Pract. 31, 27–35 - PubMed
    1. Asakawa A., Inui A., Inui T., Katsuura G., Fujino M. A., Kasuga M. (2003). Leptin treatment ameliorates anxiety in ob/ob obese mice. J. Diabetes Complicat. 17, 105–107 - PubMed
    1. Asakawa A., Inui A., Ueno N., Makino S., Fujino M. A., Kasuga M. (1999). Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice. Gastroenterology 116, 1287–1292 - PubMed
Feedback