Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats.

It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague-Dawley rats fed a high-fat diet were given the carcinogen N-methyl-N-nitrosourea and randomly assigned to vehicle (control), NPH (unmodified human insulin), glargine or detemir ( = 30 per treatment). Insulins were given subcutaneously (15 U/kg/day) 5 days a week.

Chronic Exposure to TNFα Impairs Secretion of Glucagon-Like Peptide-1.

Obesity is associated with systemic inflammation and elevated levels of TNFα, leading to impaired glucose tolerance. In humans, obesity is also associated with reduced nutrient-stimulated secretion of the intestinal incretin hormone, glucagon-like peptide-1 (GLP-1). We hypothesized that TNFα plays a direct role in the impairment of GLP-1 secretion from the enteroendocrine L-cell and that blocking TNFα can restore both GLP-1 secretion and glucose homeostasis.

Glucagon-like peptide-2 increases dysplasia in rodent models of colon cancer.

The intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances intestinal growth and reduces inflammation in rodent models. Hence, a degradation-resistant GLP-2 analog is under investigation for treatment of Crohn's disease. However, GLP-2 increases colonic dysplasia in murine azoxymethane (AOM)-induced colon cancer.