d-chiro-Inositol Attenuates Epinephrine-stimulated Hepatic Glucose Output in the Isolated Perfused Liver Independently of Insulin

Abstract

D-chiro-Inositol (DCI) is a cyclic sugar alcohol that evokes both antidiabetic and insulin sensitizing effects. Pharmacological administration of DCI has been shown to lower blood glucose in rat models of diabetes mellitus and enhance insulin sensitivity in humans with polycystic ovary syndrome (PCOS). We hypothesised that the antidiabetic effects of DCI could be due to inhibition of hepatic glucose output (HGO). To test this hypothesis, we perfused isolated rat livers either with buffer, myo-inositol, DCI, or insulin, and investigated their respective effects on the stimulation of HGO by epinephrine. We found that perfusion with 200 μM DCI attenuated epinephrine-stimulated HGO by 35% over 30 min as compared to the buffer control perfusion (p=0.05). By comparison, perfusion with 1 nM insulin attenuated epinephrine-stimulated HGO by 57% (p<0.0001). The glucose-lowering effects by DCI occurred independently of insulin and were specific to the DCI stereoisomer as 200 μM myo-inositol had no effect. These findings suggest that DCI could evoke its antidiabetic effects in vivo by inhibition of HGO. Further identification of the protein targets involved could open up new avenues to regulate hyperglycaemia with wider implications for the treatment of hepatic insulin resistance in PCOS.

Abnormalities inmyo-inositol metabolism associated with type 2 diabetes in mice fed a high-fat diet: benefits of a dietarymyo-inositol supplementation

“…The greater insulin response in the HF-MI group could also potentially arise from the effects of myo -inositol on hepatic glucose output. However, Whiting et al ( 28 ) demonstrated that myo -inositol had no insulin-like effect on epinephrine-induced hepatic glucose output. In addition, the insulin-sensitising effect of myo -inositol supplementation observed in our previous study ( 6 ) by an ITT on normally sensitive mice mainly arised from peripheral (i.e.…”

Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

“…Under general anesthesia (isoflurane 2-5%; 2 L min À1 O 2 via nasal cone), nonfasted rats underwent laparotomy between 8:00 and 9:00 AM on the experimental day. The liver was removed and quickly connected to a custommade, temperature-controlled, organ perfusion system, whereby it was perfused (in nonrecirculating mode) in a manner similar to that reported previously (Englisch et al 2000;Whiting et al 2013). Livers were perfused at a rate of 2 mL g À1 min À1 with perfusion media containing final concentrations (in mmol L À1 ): NaCl, 128; NaHCO 3 , 23.9; KCl, 6.0; CaCl 2 , 2.4; MgSO 4 , 1.18; D-glucose, 5; 3-(-Nmorpholino)propane sulfonate, 1.29; with fatty-acid-free BSA, 0.5% (w/v) at pH 7.4 gassed with O 2 :CO 2 95:5% (v/ v) at 37°C.…”

Fagopyritol, a Derivative of D-chiro-inositol, Induces GLUT4 Translocation via Actin Filament Remodeling in L6-GLUT4myc Skeletal Muscle Cells

“…Body stores, mainly in muscle and urine, of DCI gradually decrease in patients with diabetes (both type 1 and type 2) and obesity [19]. This symptom may be in part due to increased urinary losses through an unknown mechanism of DCI [33]. DCI, an inositol derivative, has been shown to act as an anti-diabetic compound by improving insulin sensitivity in patients exhibiting insulin resistance due to diabetes or polycystic ovary syndrome [1,25].…”