Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation and puncture in mice.

Sepsis is associated with high mortality. Both critically ill humans and animal models of sepsis exhibit changes in their glucose homeostasis, that is, hypoglycaemia, with the progression of infection. However, the relationship between basal glycaemia, glucose tolerance and insulin sensitivity is not well understood. Thus, we aimed to evaluate this glucose homeostasis triad at the late stage of sepsis (24 h after surgery) in male Swiss mice subjected to lethal and sublethal sepsis by the caecal ligation and puncture (CLP) model. The percentage of survival 24 h after CLP procedure in the Lethal and Sublethal groups was around 66% and 100% respectively. Both Lethal and Sublethal groups became hypoglycaemic in fasting and fed states 24 h after surgery. The pronounced fed hypoglycaemia in the Lethal group was not due to worsening anorexic behaviour or hepatic inability to deliver glucose in relation to the Sublethal group. Reduction in insulin sensitivity in CLP mice occurred in a lethality-dependent manner and was not associated with glucose intolerance. Analysis of oral and intraperitoneal glucose tolerance tests, as well as the gastrointestinal motility data, indicated that CLP mice had reduced intestinal glucose absorption. Altogether, we suggest cessation of appetite and intestinal glucose malabsorption are key contributors to the hypoglycaemic state observed during experimental severe sepsis.

Disruption of glucose tolerance caused by glucocorticoid excess in rats is partially prevented, but not attenuated, by arjunolic acid.

Arjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P > 0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent.

Glucose intolerance induced by glucocorticoid excess is further impaired by co-administration with ß-hydroxy-ß-methylbutyrate in rats.

Glucocorticoid (GC) excess alters glucose homeostasis and promotes modifications in murinometric and anthropometric parameters in rodents and humans, respectively. ß-hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, has been proposed as a nutritional strategy for preventing muscle wasting, but few data regarding its effects on glucose homeostasis are available. Here, we analyzed whether the effects of GC excess on glucose homeostasis may be attenuated or exacerbated by the concomitant ingestion of HMB. Adult Wistar rats (90-days-old) were assigned to four groups: (1) vehicle treated (Ctl), (2) dexamethasone (DEX) treated (Dex), (3) HMB treated (Hmb), and (4) DEX plus HMB treated (DexHmb). Dex groups received DEX (1 mg·kg body weight (BW)(-1), intraperitoneal) for 5 consecutive days. HMB groups ingested HMB (320 mg·kg BW(-1), oral gavage) for the same 5 days. HMB ingestion did not attenuate the effects of DEX on food intake and body weight loss, changes in masses of several organs, insulin resistance, and glucose intolerance (p > 0.05). In fact, in DexHmb rats, there was increased fasting glycemia and exacerbated glucose intolerance with the main effect attributed to DEX treatment (p < 0.05). HMB exerted no attenuating effect on plasma triacylglycerol levels from DexHmb rats, but it seems to attenuate the lipolysis induced by ß-adrenergic stimulation (20 µmol·L(-1) isoproterenol) in fragments of retroperitoneal adipose tissue from DexHmb rats. Therefore, HMB does not attenuate the diabetogenic characteristics of GC excess. In fact, the data suggest that HMB may exacerbate GC-induced glucose intolerance.