The calcitonin receptor plays a major role in glucose regulation as a function of dual amylin and calcitonin receptor agonist therapy

The Journal of Pharmacology and Experimental Therapeutics
Anna Thorsø LarsenKim Henriksen

Abstract

Amylin treatment improves body weight and glucose control, though limited by a short action and need for high doses. DACRAs are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to which extent the additional benefits reside in their higher potency or their targeting of the calcitonin receptor remains unclear. Here we deconstruct the receptors involved in the effects of a DACRA, KBP-088, by comparing it to rat amylin (rAMY), rat calcitonin (rCT) and their combination in obese HFD and diabetic ZDF rats. HFD fed Sprague Dawley rats and ZDF rats were treated for four weeks with KBP-088 (5 μg/kg/day), rAMY (300 μg/kg/day), rCT, (300 μg/kg/day) and the combination of rAMY and rCT (300+300 μg/kg/day) using infusion pumps. Body weight, food intake, fasting glycemia, HbA1c levels and glucose tolerance were assessed. In obese HFD fed rats, KBP-088, rAMY and the combination of rAMY and rCT significantly reduced body weight and improved glucose tolerance, while rCT alone had no effect. In diabetic ZDF rats, rCT was efficient in lowering fasting glycemia similar to rAMY, while dual activation by KBP-088 and the combination of rAMY and rCT were superior to activating either receptor alone....Continue Reading

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