Sustained effect of glucagon on body weight and blood glucose: Assessed by continuous glucose monitoring in diabetic rats

Abstract

Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic patients. Since the glucagon effect on blood glucose is known to be transient, it is relevant to investigate the pharmacodynamics of glucagon after repeated dosing. In the present study, we used telemetry to continuously measure blood glucose in streptozotocin induced diabetic Sprague-Dawley rats. This allowed for a more detailed analysis of glucose regulation compared to intermittent blood sampling. In particular, we evaluated the blood glucose-lowering effect of different insulin doses alone, and in combination with a long acting glucagon analog (LAG). We showed how the effect of the LAG accumulated and persisted over time. Furthermore, we found that addition of the LAG decreased body weight without affecting food intake.In a subsequent study, we focused on the glucagon effect on body weight and food intake during equal glycemic control. In order to obtain comparable maximum blood glucose lowering effect to insulin alone, the insulin dose had to be increased four times in combination with 1 nmol/kg of the LAG. In this set-up the LAG prevented further increase in body weight despite the four times higher insulin-dose. However, the body composition was changed. The insulin group increased both lean and fat mass, whereas the group receiving four times insulin in combination with the LAG only significantly increased the fat mass. No differences were observed in food intake, suggesting a direct effect on energy expenditure by glucagon. Surprisingly, we observed decreased levels of FGF21 in plasma compared to insulin treatment alone. With the combination of insulin and the LAG the blood glucose-lowering effect of insulin was prolonged, which could potentially be beneficial in diabetes treatment.

Therapeutic Effects of Pomegranate (Punica granatum L.) Juice on Liver of Diabetic Mice

“…These findings were similar to other researchers [13, 25,26]. "Decrease in body weights in DM is usually due to abnormalities of glucose metabolism and decreased of glucose uptake by body cells with subsequent shifting to adipose tissue and muscles as sources of energy that leads to weight loss" [27]. Meanwhile, the results of this study revealed that mice administered PJ for 6 weeks after induction of diabetes revealed an increase in body weight gains.…”

Protective effect of pomegranate (Punica granatum) extract against diabetic changes in adult male rat liver: Histological study

“…Decrease in body weight is usually result from disturbance of glucose metabolism and uptake by body cells with subsequent shifting to adipose tissue and muscles as sources of energy that result in weight loss. [16]…”

The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

“…Glucose deficiency leads to hypoglycemia and causes hunger. Rodents, similarly to other mammals, have glucose sensing systems in their brains responsible for regulation of food intake and glucose level homeostasis in target cells or tissues (Dauncey, 2012;Pedersen et al, 2018). In our previous study, we found that the Caprine CSN1S2 protein can safely regulate the biological mechanism in repairing ileum perforation at the doses below 2000 mg/kg BW and promote optimal functioning of microglial cell proliferation at 750 mg/kg BW (Agustina et al, 2015;Fatchiyah et al, 2017a;Rika & Fatchiyah, 2017).…”