Adiponectin Decreases Plasma Glucose and Improves Insulin Sensitivity in Diabetic Swine

Abstract

To investigate the effects of recombinant human adiponectin on the metabolism of diabetic swine induced by feeding a high-fat/high-sucrose diet (HFSD), diabetic animal models were constructed by feeding swine with HFSD for 6 months. The effects of recombinant adiponectin were assessed by detecting the change of plasma glucose levels by commercially available enzymatic method test kits and evaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinant adiponectin was produced using a 15-liter fermenter. A single injection of purified recombinant human adiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin, which triggered a transient decrease in basal glucose level (P<0.05). This effect on glucose was not associated with an increase in insulin level. Moreover, after adiponectin injection, swine also showed improved insulin sensitivity compared with the control (P<0.05). Adiponectin might have the potential to be a glucose-lowering agent for metabolic disease. Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolism could be useful to treat insulin resistance.

Adiponectin action from head to toe

“…Such a beneficial effect of adiponectin was also observed in db/db obese mice, where adiponectin reversed insulin resistance [142,233]. The same effect was observed in diabetic pigs [234]. Studies on adiponectin and insulin resistance and/or type 2 diabetes have accumulated over the years and all tend towards the conclusion that hypoadiponectinemia is highly associated with the development of those disorders and that it could be considered a risk factor in predicting the occurrence of those disorders in individuals.…”

BOARD-INVITED REVIEW: The biology and regulation of preadipocytes and adipocytes in meat animals1,2

“…Adiponectin suppresses the incorporation of glucose carbon into lipid in primary pig adipocytes (Jacobi et al, 2004). Recently, Hu et al (2007a) determined that administration of recombinant adiponectin to diabetic swine improved insulin sensitivity and enhanced glucose clearance.…”

Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes

“…As several recent studies have reported, hormones from adipose tissue play an important role in sensitizing the peripheral tissues to insulin (4, 11, 23-25, 51, 58, 64 -66). Adiponectin descreases blood glucose levels and increases insulin sensitivity without increasing insulin levels in diabetic swine (11,24,64), and may well have a role in enabling the mice in the current study to function without a detectable increase in insulin.…”

“…high sensitivity to insulin in peripheral tissues. Recent studies show evidence of specific adipokines that enhance insulin sensitivity in the peripheral tissues in the absence of increased levels of insulin (24). Furthermore, considering that the subcutaneous transplants enable a robust recovery of lost adipose tissue, it is likely that adipokines may contribute to the improved glucose homeostasis in addition to insulin in the subcutaneous transplant group.…”

“…Leptin was previously reported to improve glucose homeostasis through downregulation of resistin (4), while a recent study shows that leptin administration alone can lead to reversal of type 1 diabetes without insulin replacement (66). Adiponectin, whose levels decrease in diabetes (11,64), has been known to increase insulin sensitivity in peripheral tissues in the absence of an increase of plasma insulin levels (24). Thus, adiponectin is a likely candidate that contributes to maintaining glucose homeostasis NCRNU nude mice whose insulin levels are low (Figs.…”