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Preclinical Efficacy Evaluation in Type II Diabetes Models

Leptin is a peptide hormone secreted by adipocytes, and its expression is mainly in white adipose tissue, in addition, it is expressed in the myocardium, skeletal muscle, placenta, lung, breast epithelium and gastric mucosa. Functionally, it can inhibit appetite, increase energy expenditure, and inhibit fat synthesis to promote its decomposition. Insulin can promote the secretion of leptin, which in turn plays a negative feedback regulatory role in the synthesis and secretion of insulin.

B-ob/ob mice (Product number 110172) were generatedby knocking out exons 2 and 3 of the leptin gene using EGE technology. These mice  become obese and experience hyperglycemia symptoms and are a powerful model for studying modulators of hyperglycemia and obesity. 


Efficacy

Body weight of mice

Fasting blood glucose and non-fasting blood glucose content

Sugar tolerance test

Glucagon and insulin content


Efficacy Evaluation of Anti-Human GCGR Antibody in B-ob/ob Mice

Experimental animals: B-ob/ob mice, male, 8-10 weeks oldfrom clipboard

                            Figure 1 Efficacy of anti-human GCGR antibody drug crotedumab in B-ob/ob mice


Efficacy of the anti-human GCGR antibody drug crotedumab (synthesized in-house) in B-ob/ob mice. Male B-ob/ob mice, 8-10 weeks old, were randomly assigned to 2 groups of 6-7 animals each. Crotedumab dosing occurred on Day 0. Non-fasting blood glucose was measured on days 0, 3, and 7, and fasting blood glucose was measured after 6 hours of fasting. A) Body weight changes in B-ob/ob mice. B-C) Non-fasting blood glucose and fasting blood glucose measurements.  ( D) Crotedumab effect on glucose tolerance. E) Area under the curve of blood glucose content. Mice were fasted for 6 h with unlimited access to water, after which fasting blood glucose was measured at the tail tip (0 min).  Subsequently, glucose was injected intraperitoneally at 2 g/kg, and blood glucose was measured at the indicated times. (Fig. F-G) glucagon and insulin measurements. The results showed that crotedumab had hypoglycemic effects in both fasting and non-fasting conditions, and improved glucose tolerance in B-ob/ob mice. (Data are mean ± SEM; P ≤ 0.05, P ≤ 0.01, P ≤ 0.001)


Product list:

Product name

Product number

B-hGCGR mice

110105

B-hGLP1R mice

110106

B-ob/ob mice

110172



References

1. Katsuda, Y. et al. Diabetic mouse models. Open Journal of Animal Sciences 3, 334-342(2013).