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. 2012 Dec;16(Suppl 3):S534-42.
doi: 10.4103/2230-8210.105568.

Leptin, diabetes, and the brain

Thomas H Meek  1 , Gregory J Morton
Affiliations

Leptin, diabetes, and the brain

Thomas H Meek et al. Indian J Endocrinol Metab. 2012 Dec.

Abstract

Diabetes is a major worldwide problem. Despite some progress in the development of new antidiabetic agents, the ability to maintain tight glycemic control in order to prevent renal, retinal, and neuropathic complications of diabetes without adverse complications still remains a challenge. Recent evidence suggests, however, that in addition to playing a key role in the regulation of energy homeostasis, the adiposity hormone leptin also plays an important role in the control of glucose metabolism via its actions in the brain. This review examines the role of leptin action in the central nervous system and the mechanisms whereby leptin mediates its effects to regulate glucose metabolism. These findings suggest that defects or dysfunction in leptin signaling may contribute to the etiology of diabetes and raise the possibility that either leptin or downstream targets of leptin may have therapeutic potential for the treatment of diabetes.

Keywords: Brain; diabetes; glucose; insulin; leptin.

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Conflict of interest statement

Conflict of Interest: No

Figures

Figure 1
Figure 1
Leptin normalization of blood glucose levels in uDM. (a) Type 1 diabetes is characterized by diabetic hyperglycemia and both insulin and leptin deficiency due to the loss of pancreatic β-cells and the depletion of adipose tissue stores, respectively. This diabetic hyperglycemia is due to both reduced glucose uptake in peripheral tissues and increased rates of hepatic glucose production, in part due to increased glucagon secretion from pancreatic β-cells. (b) Leptin administration directly into the brain normalizes diabetic hyperglycemia in uDM by both potently suppressing hepatic glucose production, as well as increasing glucose uptake despite persistent severe insulin deficiency, an effect associated with normalization of elevated plasma glucagon levels.[79]
Figure 2
Figure 2
Model of CNS leptin regulation of glucose metabolism. Leptin is secreted by adipocytes, enters the CNS, and acts on its receptor expressed in key brain areas that regulate metabolism. Leptin inhibits neuropeptide and agouti-related peptide (NPY/AgRP) neurons and stimulates pro-opiomelanocortin (POMC) neurons in the ARC, responses that promote glucose uptake in peripheral tissues and the suppression of glucose production from the liver. In addition, leptin action in the VMH stimulates glucose uptake in peripheral tissues and this brain area is also implicated in the regulation of glucagon secretion. ARC, arcuate nucleus; VMH, ventromedial hypothalamus; PVN, paraventricular nucleus; Mc4r; melanocortin-4 receptor; LepRb, leptin receptor; BAT, brown adipose tissue.[104]
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