Hypoglycemia rather than vascular dysfunction causes early mortality in diabeto-septic mice

Sepsis is often complicated with pre-existing diabetes and diabetic patients are prone to infection. However, the impact of sepsis in pre-existing diabetes especially on cardio-vascular system is largely unknown. Sepsis was induced by caecal ligation and puncture while intra-peritoneal injection of streptozotocin (@ 65 mg/kg b.wt. for 5 consecutive days) was used to induce diabetes in mice. Isometric tension and mRNA expression of α _1D -adrenoceptor in aorta was determined by organ bath and qRT-PCR, respectively. Blood glucose levels and bacterial load in blood and peritoneal lavage (PL) were estimated. Histopathological examination of pancreas, lungs, liver, kidney and spleen was also done. Induction of sepsis in the mice with pre-existing diabetes caused early mortality despite being lower bacterial load in blood and PL in comparison to sepsis alone. Interestingly, NA-induced contraction as well as receptor-independent high K ⁺ -induced contraction (though significantly ( p  < 0.05) reduced in sepsis), were similar in diabeto-septic and SO groups. Accordingly, aortic mRNA expression of α _1D -adrenoceptor was also unaltered in diabeto-septic group unlike to that of sepsis where α _1D mRNA expression was significantly down-regulated. ACh-induced vasorelaxation was also unaffected in these animals. However, marked hypoglycemia before death with enhanced infiltration of inflammatory cells in lungs, liver, kidney and spleen was observed. In diabeto-septic animals, hypoglycaemia rather than vascular dysfunction was responsible for early mortality. Further, the increased infiltration of inflammatory cell in different tissues reduced the bacterial load and is responsible, at least in part, for reduction in blood glucose level leading to hypoglycemic shock.