title: Central visfatin potentiates glucose-stimulated insulin secretion and β-cell mass without increasing serum visfatin levels in diabetic rats.
abstract: BACKGROUND
  Our previous study revealed that plasma visfatin levels were lower in pregnant women with gestational diabetes (GDM) than non-GDM independent of prepreganacy BMI. We examined whether central visfatin modulates energy and glucose homeostasis via altering insulin resistance, insulin secretion or islet morphometry in diabetic rats.
  
  
  METHODS
  Partial pancreatectomized, type 2 diabetic, rats were interacerbroventricularly infused with visfatin (100ng/rat/day, Px-VIS), visfatin+visfatin antagonist, CHS-828 (100μg/rat/day, Px-VIS-ANT), or saline (control, Px-Saline) via osmotic pump, respectively, for 4weeks.
  
  
  RESULTS
  Central visfatin improved insulin signaling (pAkt→pFOXO-1) but not pSTAT3 in the hypothalamus. Central visfatin did not alter serum visfatin levels in diabetic rats whereas the levels were higher in non-diabetic rats than diabetic rats. Body weight at the 2nd week was lowered in the Px-VIS group due to decreased food intake in the first two weeks compared to the Px-Saline group and energy expenditure was not significantly different among the treatment groups of diabetic rats. Visfatin antagonist treatment nullified the central visfatin effect. Px-VIS increased whole body glucose disposal rates in euglycemic hyperinsulinemic clamp compared to Px-Saline and lowered hepatic glucose output, whereas Px-VIS-ANT blocked the visfatin effect on insulin resistance (P<0.05). In hyperglycemic clamp study, the area under the curve of insulin in first and second phase were significantly higher in the Px-VIS group than the Px-Saline group without modifying insulin sensitivity at the hyperglycemic state, whereas the increase in serum insulin levels was blocked in the Px-VIS-ANT group. Central visfatin also increased β-cell mass by increasing β-cell proliferation.
  
  
  CONCLUSIONS
  Central visfatin improved glucose homeostasis by increasing insulin secretion and insulin sensitivity at euglycemia through the hypothalamus in diabetic rats. Therefore, visfatin is a positive modulator of glucose homeostasis by delivering the hypothalamic signals into the peripheries.
authors: Food & Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, Republic of Korea.
authors: Da Sol
authors: DS
authors: Kim
authors: Food & Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, Republic of Korea.
authors: Suna
authors: S
authors: Kang
authors: Food & Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, Republic of Korea.
authors: Na Rang
authors: NR
authors: Moon
authors: Food & Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, Republic of Korea. Electronic address: smpark@hoseo.edu.
authors: Sunmin
authors: S
authors: Park
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000201:enzymology* / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D054409:Nicotinamide Phosphoribosyltransferase; D005947:Glucose
keywords: Energy; Glucose; Insulin; Visfatin; Visfatin antagonist