TABLE 3.

Tissue-specific effects of adipokines on glucose homeostasis

Adipokine	Effect on Food/Fat Intake or Central Nervous System	Hepatic Glucose Production	Glucose Disposal/Tolerance in Muscle and/or Adipose	Beta Cell Survival and Insulin Production
Leptin	Anorexigenic	Enhances insulin sensitivity via AMPK	Enhances insulin sensitivity in muscle via AMPK and decreases intracellular lipid levels	As part of “adipo-insular” feedback loop, inhibits insulin release by inhibiting proinsulin synthesis and insulin secretion; may have a role in β-cell survival; in obesity, leptin resistance may impair the protective mechanism
Adiponectin	No effect on food intake, but ICV leads to increased energy expenditure; present in human cerebrospinal fluid	Enhances insulin sensitivity via AMPK	Mixed results; increases insulin action to no effect at all	No effect on insulin synthesis and secretion in healthy subjects but may improve insulin secretion in HFD models
TNF-α	Anorexigenic	Reduces insulin signaling in rodents; no direct effect in healthy humans infused with TNF-α	Reduces insulin-stimulated glucose uptake by white adipose tissue and muscle; multiple mechanisms include serine phosphorylation of IRS-1 and AS160, activation of several serine kinases including JNK and AMPK, NF-κB activation, SOCS3 expression, Glut4 suppression, and ROS production	Multiple effects in vitro from impairing glucose-stimulated insulin secretion to apoptosis; in vivo role in obesity unclear; may play a role in β-cell failure; however, the expression of TNF-α in the pancreas of transgenic mice without obesity resulted in insulitis, not diabetes
IL-6	Anorexigenic	Reduces insulin sensitivity by inhibition of insulin receptor signal transduction, at least in part by expression of SOCS-3	Conflicting data: both promoting glucose uptake and inhibitory with similar action to TNF-α	Role in obesity unclear; may play a protective role in β-cell hyperplasia, in that expression of IL-6 in the pancreas of transgenic mice resulted in islet hyperplasia and insulitis
Resistin	Potentially anorexigenic; present in human cerebrospinal fluid	Reduces insulin sensitivity; increases glucose output–primary effect	Reduces glucose uptake but not as dramatic as action on liver	Impairs glucose-stimulated insulin secretion in vitro
RBP4	Unknown	Reduces insulin sensitivity; is gluconeogenic via PEPCK activation	Impaired insulin action in muscle mechanism not clear	Unknown
PBEF/visfatin	Unknown	Unclear	Enhances via insulin receptor	Potential role in β-cell survival, as circulating visfatin is increased with progressive β-cell deterioration
Omentin (humans, not mice)	Unknown	Unknown	Enhances insulin-stimulated signals and glucose uptake but not insulin-mimetic	Unknown

AMPK, adenosine mono phosphate-activated protein kinase; HFD, high fat diet; ICV, intracerebroventricular; PEPCK, phosphoenolpyruvate carboxykinase; SOCS-3, suppressor of cytokine signalling-3.