| Summary: | 碩士 === 國立臺灣大學 === 動物科學技術學研究所 === 102 === Type 1 diabetes (T1D) is an autoimmune disease, which characterized by progressive dysfunction of pancreatic β cell and loss in β cell mass. The disease generally results in insulin deficiency and hyperglycemia. Glucagon-like peptide-1 (GLP-1) is a gut hormone which secreted by enteroendocrine cell. It has been well documented that GLP-1 could regulate β cell growth and increase insulin secretion to maintain glucose homeostasis. Therefore, our aim was to screen and select lactic acid bacteria (LAB) with abilities to stimulate intestinal GLP-1 secretion.
The murine enteroendocrine STC-1 cells were co-cultured with sixty LABs at a ratio of 1: 100 and GLP-1 productions in supernatant were measured. We selected and identified top two strains, Lactobacillus kefiranofaciens and Lactobacillus kefiri, significantly elevating GLP-1 secretion when compared with control group (p< 0.05). We next investigated GLP-1 secretion abilities and improvement of hyperglycemia in vivo. Four-week-old male C57BL/6 mice were induced diabetes by intraperitoneal injection of streptozotocin(STZ) for 4 consecutive days. Diabetic mice were randomly assigned to different groups and were administered PBS or selected two strains 108 CFU per mouse daily for eight weeks. The results exhibited that Lb. kefiranofaciens and Lb. kefiri could significantly lower fasting blood glucose than STZ group after eight week administration. Lb. kefiri also significantly improve glucose homeostasis after oral glucose challenge when compared with the STZ group. We found that Lb. kefiranofaciens and Lb. kefiri group showed significantly higher insulin/pancreas ratio by pancreas immunohistochemistry staining. Modulation effects on cytokines level and an elevation of serum GLP-1 levels were also observed. However, administration of Lb. kefiri did not show significant effect to delay the onset of diabetes in non obese diabetic (NOD) mice. We further tried to address possible mechanism and found that toll-like receptor 2 and short chain fatty acid production might be not involved in blood glucose lowering effect.
Taken together, our present study concluded that Lb. kefiranofaciens and Lb. kefiri could stimulate GLP-1 secretion both in vitro and in vivo. Oral administration of Lb. kefiranofaciens and Lb. kefiri provided a benefit to blood glucose homeostasis in STZ-induced T1D model. It suggested that the selected strains might be a potential therapeutic supplementation to T1D. However, the mechanisms need more clarification.
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