Journal article
The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity : KBP-042, a Weight Loss Drug and Insulin Sensitizer
Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s.c. administrations for 56 days, and glucose tolerance was assessed after one acute injection, 3 weeks of treatment, and again after 7 weeks of treatment.
To assess the effect on insulin sensitivity, rats received 5 μg/kg KBP-042 for 21 days before hyperinsulinemic-euglycemic clamp. Results: KBP-042 induced a sustained weight loss of up to 20% without any significant weight reduction in the pair-fed groups. Decreases in adipose tissues and lipid deposition in the liver were observed, while plasma adiponectin was increased and plasma leptin levels were decreased.
Acute administration of KBP-042 led to impaired glucose tolerance and increased plasma lactate, while this diabetogenic effect was reversed by chronic treatment. Finally, assessment of insulin sensitivity using the hyperinsulinemic-euglycemic clamp showed that KBP-042 increased the glucose infusion rate.
Conclusions: The study indicates that KBP-042 combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance.
Language: | English |
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Publisher: | Wiley |
Year: | 2016 |
Pages: | 1712-1722 |
ISSN: | 1930739x and 19307381 |
Types: | Journal article |
DOI: | 10.1002/oby.21563 |