Understanding Liver Inflammation due to Gut Microfloral Alteration in Diet Induced Diabetes

Abstract

Liver is a main organ for metabolism of sugars, particularly sucrose and fructose. High Sugar flux leads to enhanced hepatic triglyceride accumulation resulting in impaired glucose & lipid metabolism and increase pro-inflammatory cytokine expression which shows decrease insulin sensitivity and increase inflammation. We have hypothesized that giving a treatment of colon targeted gram-negative antibiotic they may help to decrease the chances of inflammation. Our main objective is to study the role of gene involved in carbohydrate metabolism and other gene expressions in liver. Our project model was mice (C57BL/6), which were fed with high sugar diet to induce diabetes. OGTT was performed to check glucose tolerance. Control and HSD group of animals were dissected once they became diabetic. Animals were sacrificed; their blood, fecal and tissue sample were collected and performed various test like biochemical analysis, gene expression analysis, histopathology analysis. Other two groups of diabetic mice were then treated with gram negative antibiotic in form of API and microsphere. Cefdinir microsphere coated with polymer which specifically target the colon. Both the treatment groups were sacrificed following 30 days of treatment. Following autopsy all the parameters similar to HSD groups were also carried out in these groups. Various parameters were checked to understand effect of treatment on various tissues of the diabetic mice. Our investigation showed that after biochemical assays such as TG, Cholesterol, SGPT, SGOT, Insulin, FFA test its level has significantly increased in HSD group and reversal effect was observed in antibiotic treated HSD group. Gene expression study showed altered TLRs, GPRs, PPARs, level which indicate that there is significant changes occur between HSD group and antibiotic treated HSD group. Treating diabetic mice with gram negative antibiotic decreases gram negative bacterial population which lowered inflammatory condition and thus increase insulin sensitivity. In our investigation crude is more effective because of its potency and colon targeted antibiotic treatment (Microsphere) is easy way to cure diabetes in longterm treatment. This effect can be more prominent if the period of treatment could prolong to 30days.