Limits...
The role of leptin in glucose homeostasis.

Denroche HC, Huynh FK, Kieffer TJ - J Diabetes Investig (2012)

Bottom Line: However, there is now substantial evidence that leptin also plays a primary role in the regulation of glucose homeostasis, independent of actions on food intake, energy expenditure or body weight.The mechanisms through which leptin modulates glucose metabolism have not been fully elucidated.Leptin receptors are widely expressed in peripheral tissues, including the endocrine pancreas, liver, skeletal muscle and adipose, and both direct and indirect leptin action on these tissues contributes to the control of glucose homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Physiological Sciences, The Life Sciences Institute.

ABSTRACT
The fat-derived hormone, leptin, is well known to regulate body weight. However, there is now substantial evidence that leptin also plays a primary role in the regulation of glucose homeostasis, independent of actions on food intake, energy expenditure or body weight. As such, leptin might have clinical utility in treating hyperglycemia, particularly in conditions of leptin deficiency, such as lipodystrophy and diabetes mellitus. The mechanisms through which leptin modulates glucose metabolism have not been fully elucidated. Leptin receptors are widely expressed in peripheral tissues, including the endocrine pancreas, liver, skeletal muscle and adipose, and both direct and indirect leptin action on these tissues contributes to the control of glucose homeostasis. Here we review the role of leptin in glucose homeostasis, along with our present understanding of the mechanisms involved. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00203.x, 2012).

No MeSH data available.


Related in: MedlinePlus

 Centrally‐mediated actions of leptin on tissues that contribute to glucose homeostasis. Leptin activates leptin‐responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin sensitive tissues through autonomic efferents. The sympathetic nervous system has been implicated in central leptin action on insulin secretion, and glucose metabolism in brown adipose tissue, skeletal muscle and the liver. The parasympathetic nervous system might mediate effects of central leptin on hepatic insulin sensitivity and glycogenolysis. It is unclear which autonomic system mediates leptin action on glucagon secretion and the inhibition of insulin signaling in white adipose tissue. AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; PNS, parasympathetic nervous system; SNS, sympathetic nervous system; WAT, white adipose tissue.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4020728&req=5

f2:  Centrally‐mediated actions of leptin on tissues that contribute to glucose homeostasis. Leptin activates leptin‐responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin sensitive tissues through autonomic efferents. The sympathetic nervous system has been implicated in central leptin action on insulin secretion, and glucose metabolism in brown adipose tissue, skeletal muscle and the liver. The parasympathetic nervous system might mediate effects of central leptin on hepatic insulin sensitivity and glycogenolysis. It is unclear which autonomic system mediates leptin action on glucagon secretion and the inhibition of insulin signaling in white adipose tissue. AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; PNS, parasympathetic nervous system; SNS, sympathetic nervous system; WAT, white adipose tissue.

Mentions: Evidence suggests that leptin also inhibits insulin secretion through central mechanisms (Figure 2). Mice with neuronal disruption of leptin signaling show hyperinsulinemia, whether body weight is unaltered109 or increased110. Intracerebroventricular (ICV) administration of leptin either as a peptide or as a gene therapy lowers insulin levels111–115, although in one study the effect was modest116, whereas in another, leptin did not lower meal‐stimulated insulin levels compared with pair‐fed controls43. The effect of central leptin action on insulin levels is consistent with increased sympathetic tone to β‐cells. Indeed, a recent study showed that acute ICV leptin administration suppressed glucose‐stimulated insulin secretion in a manner dependent on activation of the sympathetic nervous system (SNS)113. One SNS‐mediated mechanism of leptin action on the β‐cell has been proposed to occur through sympathetic inhibition of bioactive osteocalcin secretion from osteoblasts, which in turn reduces β‐cell insulin secretion109. Interestingly, one study found that an inhibitory effect of leptin on glucose stimulated insulin secretion was observed in vagotomized, but not intact rats, and was abolished by sympathectomy117. Thus, although studies indicate that the SNS partly mediates the inhibitory action of leptin on β‐cells, this might be counterbalanced by the parasympathetic nervous system (PNS).


The role of leptin in glucose homeostasis.

Denroche HC, Huynh FK, Kieffer TJ - J Diabetes Investig (2012)

 Centrally‐mediated actions of leptin on tissues that contribute to glucose homeostasis. Leptin activates leptin‐responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin sensitive tissues through autonomic efferents. The sympathetic nervous system has been implicated in central leptin action on insulin secretion, and glucose metabolism in brown adipose tissue, skeletal muscle and the liver. The parasympathetic nervous system might mediate effects of central leptin on hepatic insulin sensitivity and glycogenolysis. It is unclear which autonomic system mediates leptin action on glucagon secretion and the inhibition of insulin signaling in white adipose tissue. AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; PNS, parasympathetic nervous system; SNS, sympathetic nervous system; WAT, white adipose tissue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020728&req=5

f2:  Centrally‐mediated actions of leptin on tissues that contribute to glucose homeostasis. Leptin activates leptin‐responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin sensitive tissues through autonomic efferents. The sympathetic nervous system has been implicated in central leptin action on insulin secretion, and glucose metabolism in brown adipose tissue, skeletal muscle and the liver. The parasympathetic nervous system might mediate effects of central leptin on hepatic insulin sensitivity and glycogenolysis. It is unclear which autonomic system mediates leptin action on glucagon secretion and the inhibition of insulin signaling in white adipose tissue. AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; PNS, parasympathetic nervous system; SNS, sympathetic nervous system; WAT, white adipose tissue.
Mentions: Evidence suggests that leptin also inhibits insulin secretion through central mechanisms (Figure 2). Mice with neuronal disruption of leptin signaling show hyperinsulinemia, whether body weight is unaltered109 or increased110. Intracerebroventricular (ICV) administration of leptin either as a peptide or as a gene therapy lowers insulin levels111–115, although in one study the effect was modest116, whereas in another, leptin did not lower meal‐stimulated insulin levels compared with pair‐fed controls43. The effect of central leptin action on insulin levels is consistent with increased sympathetic tone to β‐cells. Indeed, a recent study showed that acute ICV leptin administration suppressed glucose‐stimulated insulin secretion in a manner dependent on activation of the sympathetic nervous system (SNS)113. One SNS‐mediated mechanism of leptin action on the β‐cell has been proposed to occur through sympathetic inhibition of bioactive osteocalcin secretion from osteoblasts, which in turn reduces β‐cell insulin secretion109. Interestingly, one study found that an inhibitory effect of leptin on glucose stimulated insulin secretion was observed in vagotomized, but not intact rats, and was abolished by sympathectomy117. Thus, although studies indicate that the SNS partly mediates the inhibitory action of leptin on β‐cells, this might be counterbalanced by the parasympathetic nervous system (PNS).

Bottom Line: However, there is now substantial evidence that leptin also plays a primary role in the regulation of glucose homeostasis, independent of actions on food intake, energy expenditure or body weight.The mechanisms through which leptin modulates glucose metabolism have not been fully elucidated.Leptin receptors are widely expressed in peripheral tissues, including the endocrine pancreas, liver, skeletal muscle and adipose, and both direct and indirect leptin action on these tissues contributes to the control of glucose homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Physiological Sciences, The Life Sciences Institute.

ABSTRACT
The fat-derived hormone, leptin, is well known to regulate body weight. However, there is now substantial evidence that leptin also plays a primary role in the regulation of glucose homeostasis, independent of actions on food intake, energy expenditure or body weight. As such, leptin might have clinical utility in treating hyperglycemia, particularly in conditions of leptin deficiency, such as lipodystrophy and diabetes mellitus. The mechanisms through which leptin modulates glucose metabolism have not been fully elucidated. Leptin receptors are widely expressed in peripheral tissues, including the endocrine pancreas, liver, skeletal muscle and adipose, and both direct and indirect leptin action on these tissues contributes to the control of glucose homeostasis. Here we review the role of leptin in glucose homeostasis, along with our present understanding of the mechanisms involved. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00203.x, 2012).

No MeSH data available.


Related in: MedlinePlus