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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

 Direct actions of leptin on tissues that contribute to glucose homeostasis. Leptin acts on peripheral leptin receptor‐b isoform expressing tissues, including the endocrine pancreas and insulin‐sensitive tissues. Direct leptin action on the endocrine pancreas inhibits insulin secretion from β‐cells, and glucagon secretion from α‐cells. Leptin acts on adipocytes to suppress insulin signaling and action, and in vivo studies indicate that leptin directly antagonizes hepatic insulin sensitivity. Direct leptin action on skeletal muscle can either increase or decrease glucose uptake and insulin stimulated glucose metabolism, and the overall effect remains controversial (combined up and down arrow). AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; cAMP, cyclic adenosine monophosphate; WAT, white adipose tissue.
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f1:  Direct actions of leptin on tissues that contribute to glucose homeostasis. Leptin acts on peripheral leptin receptor‐b isoform expressing tissues, including the endocrine pancreas and insulin‐sensitive tissues. Direct leptin action on the endocrine pancreas inhibits insulin secretion from β‐cells, and glucagon secretion from α‐cells. Leptin acts on adipocytes to suppress insulin signaling and action, and in vivo studies indicate that leptin directly antagonizes hepatic insulin sensitivity. Direct leptin action on skeletal muscle can either increase or decrease glucose uptake and insulin stimulated glucose metabolism, and the overall effect remains controversial (combined up and down arrow). AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; cAMP, cyclic adenosine monophosphate; WAT, white adipose tissue.

Mentions: Leptin binding, Lepr‐b transcript expression, and functional Lepr‐b signaling have been shown in pancreatic islets or β‐cells from mice, rats and humans80,81,83–85. In vitro studies support a direct suppressive action of leptin on basal‐ and glucose‐stimulated insulin gene expression and secretion in β‐cells (Figure 1)44,79–81,84–88. Leptin robustly inhibits insulin secretion from isolated islets and the perfused pancreas of ob/ob mice80,84. Most studies using islets or perfused pancreata from non‐leptin deficient animals, and β‐cell lines show an inhibitory effect of leptin on insulin secretion79,80,86,89–93, although in a few reports leptin administration had no effect87,94–96, or even stimulated97,98 insulin secretion. The reasons for these apparent discrepancies are not clear.


The role of leptin in glucose homeostasis.

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

 Direct actions of leptin on tissues that contribute to glucose homeostasis. Leptin acts on peripheral leptin receptor‐b isoform expressing tissues, including the endocrine pancreas and insulin‐sensitive tissues. Direct leptin action on the endocrine pancreas inhibits insulin secretion from β‐cells, and glucagon secretion from α‐cells. Leptin acts on adipocytes to suppress insulin signaling and action, and in vivo studies indicate that leptin directly antagonizes hepatic insulin sensitivity. Direct leptin action on skeletal muscle can either increase or decrease glucose uptake and insulin stimulated glucose metabolism, and the overall effect remains controversial (combined up and down arrow). AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; cAMP, cyclic adenosine monophosphate; WAT, white adipose tissue.
© Copyright Policy
Related In: Results  -  Collection

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

f1:  Direct actions of leptin on tissues that contribute to glucose homeostasis. Leptin acts on peripheral leptin receptor‐b isoform expressing tissues, including the endocrine pancreas and insulin‐sensitive tissues. Direct leptin action on the endocrine pancreas inhibits insulin secretion from β‐cells, and glucagon secretion from α‐cells. Leptin acts on adipocytes to suppress insulin signaling and action, and in vivo studies indicate that leptin directly antagonizes hepatic insulin sensitivity. Direct leptin action on skeletal muscle can either increase or decrease glucose uptake and insulin stimulated glucose metabolism, and the overall effect remains controversial (combined up and down arrow). AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; cAMP, cyclic adenosine monophosphate; WAT, white adipose tissue.
Mentions: Leptin binding, Lepr‐b transcript expression, and functional Lepr‐b signaling have been shown in pancreatic islets or β‐cells from mice, rats and humans80,81,83–85. In vitro studies support a direct suppressive action of leptin on basal‐ and glucose‐stimulated insulin gene expression and secretion in β‐cells (Figure 1)44,79–81,84–88. Leptin robustly inhibits insulin secretion from isolated islets and the perfused pancreas of ob/ob mice80,84. Most studies using islets or perfused pancreata from non‐leptin deficient animals, and β‐cell lines show an inhibitory effect of leptin on insulin secretion79,80,86,89–93, although in a few reports leptin administration had no effect87,94–96, or even stimulated97,98 insulin secretion. The reasons for these apparent discrepancies are not clear.

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