Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells

Abstract

AIMTo assess in rodent and human adipocytes the antilipolytic capacity of hexaquis(benzylammonium) decavanadate (B6V10), previously shown to exert antidiabetic effects in rodent models, such as lowering free fatty acids (FFA) and glucose circulating levels.METHODSAdipose tissue (AT) samples were obtained after informed consent from overweight women undergoing plastic surgery. Comparison of the effects of B6V10 and reference antilipolytic agents (insulin, benzylamine, vanadate) on the lipolytic activity was performed on adipocytes freshly isolated from rat, mouse and human AT. Glycerol release was measured using colorimetric assay as an index of lipolytic activity. The influence of B6V10 and reference agents on glucose transport into human fat cells was determined using the radiolabelled 2-deoxyglucose uptake assay.RESULTSIn all the species studied, B6V10 exhibited a dose-dependent inhibition of adipocyte lipolysis when triglyceride breakdown was moderately enhanced by β-adrenergic receptor stimulation. B6V10 exerted on human adipocyte a maximal lipolysis inhibition of glycerol release that was stronger than that elicited by insulin. However, B6V10 did not inhibit basal and maximally stimulated lipolysis. When incubated at dose ≥ 10 μmol/L, B6V10 stimulated by twofold the glucose uptake in human fat cells, but - similarly to benzylamine - without reaching the maximal effect of insulin, while it reproduced one-half of the insulin-stimulation of lipogenesis in mouse fat cells.CONCLUSIONB6V10 exerts insulin-like actions in adipocytes, including lipolysis inhibition and glucose transport activation. B6V10 may be useful in limiting lipotoxicity related to obesity and insulin resistance.

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

“…The obtained hypoglycemic effect of the investigated polyoxotungstates is in agreement with previously published in vivo studies that reported effective hypoglycemic actions of various types of polyoxotungstates on different diabetic animal models. [7][8][9] According to literature, a few putative mechanisms of POM induced normoglycemic action were indicated: a-glucosidase activity inhibition that consequently results in the reduced absorption of intestinal carbohydrates, 8 insulin mimetic effects including glucose uptake stimulation and lipolysis inhibition, 27 prevention of STZ-induced apoptosis of pancreatic b-cells, and stimulation of insulin synthesis. 7 Moreover, some polyoxotungstates were found to prevent the development of diabetic life-threatening microvascular and macrovascular complications by signicant limitation of aldose reductase activities and accumulation of advanced glycation end products.…”

Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets

“…The adipocyte preparations used in the present study were obtained from a total of 56 women of a mean age of 40 years with a mean body mass index (BMI) of 25. The fat cells were immediately subjected to hexose uptake assays as described below since freezing/thawing sequences are not compatible with the preparation of functional adipocytes, as described in [36].…”

Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

“…Again, insulin did not significantly inhibit isoprenaline-stimulated lipolysis in this second set of experiments, that is, when tested at 100 nM against equivalent dose of isoprenaline (Figure 4). This is not so inconsistent, as human adipocytes are recognized as being less insulin-sensitive than rodent fat cells, especially in the case of overweight individuals [40]. Nevertheless, the presence of opipramol did not alter the antilipolytic effect of insulin-there was neither worsening nor addition of their effects when the two agents were tested simultaneously.…”