| Obese patients with type II diabetes whose high blood glucose and insulin tolerance would get high improvement after bariatric surgery. Diabetic mouse that undergo a duodeno-jejunal bypass (DJB) procedure, which maintains the gastric volume intact while bypassing the entire duodenum and the proximal jejunum, show similar improvements in their diabetes. However, the physiological mechanisms by which the surgery improves the diabetic state are not known.In this study, we used a diabetic mouse model---TIMO(Transgenic Insertion Mutants with Obesity) mice to investigate glucose homeostasis and morphological changes in the bypassed duodenum-jejunum and other metabolic organ---liver, muscle, white adiposity tissue and brown adiposity tissue. TIMO mice exhibited early development of obesity and type â…¡ diabetes, in which a potential regulatory locus lies 857 kb upstream of Brain-derived neurotropic factor (Bdnf) was disrupted by transgene insertion. To according with that BDNF is vital for glucose homeostasis and food intake regulation both in human and mice. TIMO mice exhibited higher food intake with lower BDNF level in hypothalamus compared to its wild type littermates. Meanwhile the inflammation level also increased with body weight in different tissues of TIMO mice.We identified that TIMO mice demonstrated improved glucose tolerance and decreased fasting blood glucose after duodeno-jejunum gastric bypass (DJB) surgery, similar to findings after bariatric surgery in obese patients with type â…¡ diabetes. Interestingly, there were no changes in the food intake and heat production in the normal mice after DJB groups, while DJB surgery can dramatic improve the type II diabetes in mice, suggesting that bariatric surgery cannot affect the normal mice with normal glucose levels and insulin tolerance.To further study the role of inflammation result from obesity during the development of diabetes, we suppose that the glucose and insulin improvement owing to the systemic inflammation alleviation. It reported that gut microbiota change after duodenum-jejunum gastric bypass may also involve in metabolism improvement. Researches on TIMO mice after DJB operation indicated that inflammation remission may result in obesity and type II diabetes resolution. Meanwhile biochemistry result demonstrated that lipid metabolism ameliorated post DJB operation also contributed to diabetes therapy.In summary, our data suggested that DJB operation can alleviate diabetes in mouse model through improving its glucose homeostasis, insulin sensitivity and lipid metabolism. Beside above all, whether commensal dysbiosis in TIMO mice lead to inflammation which contributed to diabetes is still need more study. |
