Glucosamine infusion in rats mimics the β-cell dysfunction of non—insulin-dependent diabetes mellitus

Effects of glucosamine infusion on insulin secretion and insulin action in humans.

“…2) in an attempt to prove that it can blunt the -c e l l response to glucose in vivo. At variance with previous studies conducted in the rat (17, 37,38), no alterations of the -c e l l secretory pattern were observed during either the low-or the high-GlcN studies. However, GlcN shifted the -cell glucose threshold to the right (Fig.…”

“…GlcN has long been known to be an inhibitor of glucokinase (35)(36)(37), the glucose sensor of the -cell. Accordingly, GlcN in vivo can reduce the first and second phases of insulin secretion in the rat (17,37,38), suggesting that it can fully mimic the detrimental effect of prolonged glucose exposure on insulin action and secretion (17,38).…”

Hexosamines stimulate apoptosis by altering SIRT1 action and levels in rodent pancreatic -cells

“…Rate-limiting enzymes in the HBP are glutamine: fructose-6-phosphate amidotransferase (GFAT), which catalyzes the formation of glucosamine-6-phosphate from fructose-6-phosphate and glutamine, and O-glucosamine acetyl transferase, which adds a UDP-acetylglucosamine group to a target protein and is overexpressed in pancreas. Adipocytes (Considine et al 2000), fibroblasts, and rodents (Brownlee et al 1988, Shankar et al 1998, Veerababu et al 2000, Einstein et al 2008 exposed to glucosamine, which directly enters and stimulates the HBP, develop insulin resistance. In addition, HBP activation induces defects in insulin production and secretion by attenuating the activity of glucokinase in b-cells (Balkan & Dunning 1994, Shankar et al 1998, Yoshikawa et al 2002.…”

“…Adipocytes (Considine et al 2000), fibroblasts, and rodents (Brownlee et al 1988, Shankar et al 1998, Veerababu et al 2000, Einstein et al 2008 exposed to glucosamine, which directly enters and stimulates the HBP, develop insulin resistance. In addition, HBP activation induces defects in insulin production and secretion by attenuating the activity of glucokinase in b-cells (Balkan & Dunning 1994, Shankar et al 1998, Yoshikawa et al 2002. Similar to animals exposed to glucosamine, transgenic animals overexpressing GFAT either in skeletal muscle, fat, or in liver also develop insulin resistance (Hebert et al 1996, Veerababu et al 2000.…”

Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6-phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine

“…Thus, there has been growing interest in a role for glucosamine in mediating insulin resistance in diabetes mellitus [14,15]. It was recently reported that intravenous infusion of glucosamine, which enters cells via glucose transporters for conversion into glucosamine-6-P, considerably reduced blood flow in hind limb femoral muscles of normoglycaemic rats [16].…”