Amylin exerts osteogenic actions with different efficacy depending on the diabetic status.

Amylin displays osteogenic features, but its role in diabetic osteopenia is unclear. We examined the possible osteogenic action of amylin infusion for 3days into fructose-induced insulin-resistant (IR) and streptozotocin-induced type 2 diabetic (T2D) and normal (N) rats. Amylin failed to affect glycaemia or parathyroid hormone levels in any group, but reduced hyperinsulinemia in IR rats. In N rats, amylin increased bone formation rate and reduced osteoclast surface and erosive surface in the femoral metaphysis, and increased osteoprotegerin (OPG)/receptor activator of NFκB ligand (RANKL) mRNA ratio in the tibia. In T2D rats, amylin normalized trabecular structure parameters and increased osteoblast number and osteocalcin (OC) expression in long bones. In contrast, in IR rats, no apparent osteogenic effect of amylin in the femur was observed, although both OC and OPG/RANKL ratio were increased in the tibia. Our findings demonstrate a different osteogenic efficacy of amylin in two diabetic settings.

Amylin effect in extrapancreatic tissues participating in glucose homeostasis, in normal, insulin-resistant and type 2 diabetic state.

Amylin is co-secreted with insulin, responds to the same stimuli, is anorectic, lowers body weight by reducing fat mass, and is proposed for diabetes treatment. We examined the effect of a 3-day constant infusion of close to physiological doses of amylin in Wistar rats, on glucotransporter expression, glycogen content (G), glycogen synthase a activity (GSa) and glucose transport (GT), in liver, muscle and fat from insulin resistant (IR) and type 2 diabetic (T2D) models, compared to normal (N) animals; plasma glucose and insulin were measured. Plasma insulin in IR was higher than in N or T2D, and amylin normalized the value. In both, IR and T2D, liver G was lower than normal, accompanied by GLUT-2, mRNA and protein, higher and lower, respectively, than in N; amylin normalized G in both groups, without changes in GLUT-2, except for an mRNA increase in T2D. In IR and T2D, muscle GSa was reduced, together with respective over- and under-GLUT-4 expression; amylin induced only a trend toward GSa normalization in both groups. In isolated adipocytes, GT and GLUT-4 in IR and T2D were lower and higher, respectively, than in N; after amylin, not only GT was normalized in both groups but also the response to insulin was much more pronounced, including that in N, without major changes in GLUT-4. This suggests that the beneficial effect of amylin in states running with altered glucose homeostasis could occur by partially acting on the hexose metabolism of the liver and mainly on that of the adipose tissue.