Dyslipidaemia and dysglycaemia in HIV-infected patients on highly active anti-retroviral therapy in Kumasi Metropolis.

BACKGROUND: Diet and genetic predisposition significantly affect lipid metabolism in the individual. This metabolic effect is further challenged in patients infected with HIV and on HAART. The prolonged use of HAART is associated with lipodystrophy, dyslipidemia, and insulin resistance. OBJECTIVE: To determine the prevalence of lipid dysregulation and dysglycaemia in HIV infected patients on HAART in the Kumasi metropolis. METHODS: This cross sectional study was conducted between October 2009 and June 2010, and 305 HIV-infected patients consisting of 164 patients on HAART for at least six months and 141 HAART-naive patients constituted HIV-positive patients, not on HAART and whose CD4 were not below 320 cell/ml as the control. Data was analyzed using Graph Pad Prism (version 5.0). Unpaired t-test, linear and multivariate regression analyses, was used to predict glucose level from the various parameters. Anthropometric parameters consisting of body weight, waist and hip circumferences, height, bicep and triceps skin fold were measured with a pair of calipers. Lipid profile and fasting blood glucose were determined by enzymatic methods. CD4 counts and hemoglobin were determined. RESULTS: Fasting plasma, glucose (3.81±0.08mmol/l, 4.48±0.17mmol/l), total cholesterol (3.05± 0.0 8mmol/l, 4.54±0.08mmol/l) LDL (2.24±0.07mmol/l, 2.87±0.07mmol/l) and HDL (0.85±0.04mmol/l, 0.97±0.03mmol/l) between the control and case respectively were significantly raised (P< 0.001), though within the physiological range. The significantly increased hip and waist circumferences, waist-to-hip ratio (0.85±0.22, 0.88±0.01) of the control and case correlated with lipodystrophy. CONCLUSION: HAART was associated with lipodystrohy and, the risk of developing type II diabetes among the HAART experienced group was 5 times higher than the HAART naive group.

A new, highly selective murine peroxisome proliferator-activated receptor δ agonist increases responsiveness to thermogenic stimuli and glucose uptake in skeletal muscle in obese mice.

AIM: We investigated how GW800644, the first pharmacologically selective murine peroxisome proliferator-activated receptor δ (PPARδ) agonist, affects energy balance, glucose homeostasis and fuel utilization by muscle in obese mice. METHODS: Potencies were determined in transactivation assays. Oral glucose tolerance was determined after 14 and 22 days' administration (10 mg/kg body weight, twice daily) to Lep(ob)/Lep(ob) mice. Food intake and energy expenditure were measured during a 26-day experiment, and plasma metabolites and 2-deoxyglucose uptake in vivo at termination. Palmitate oxidation and 2-deoxyglucose uptake by isolated soleus muscles were measured after 14 (in lean and obese mice) and 26 days. RESULTS: GW800644 activated murine PPARδ (EC(50) 2 nM), but caused little to no activation of PPARα or PPARγ up to 10 µM. It did not increase liver weight. GW800644 reduced food intake and body weight in obese mice after 8 days. It did not affect resting energy expenditure, but, compared to pair-fed mice, it increased the response to a ß(3)-adrenoceptor agonist. It improved glucose tolerance. GW800644, but not pair-feeding, reduced plasma glucose, insulin and triglyceride concentrations. It increased 2-deoxyglucose uptake in vivo in adipose tissue, soleus muscle, heart, brain and liver, and doubled 2-deoxyglucose uptake and palmitate oxidation in isolated soleus muscle from obese but not lean mice. CONCLUSIONS: PPARδ agonism reduced food intake and independently elicited metabolic effects that included increased responsiveness to ß(3)-adrenoceptor stimulation, increased glucose utilization and fat oxidation in soleus muscle of Lep(ob)/Lep(ob) but not lean mice and increased glucose utilization in vivo in Lep(ob)/Lep(ob) mice.

Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and beta2-adrenoceptor mechanisms.

BACKGROUND AND PURPOSE: Picomolar concentrations of the beta3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via beta2-adrenoceptors. Effects of BRL37344 and beta2-adrenoceptor agonists are compared. EXPERIMENTAL APPROACH: Mouse soleus muscles were incubated with 2-deoxy[1-(14)C]-glucose, [1-(14)C]-palmitate or [2-(14)C]-pyruvate, and BRL37344, beta2-adrenoceptor agonists and selective beta-adrenoceptor antagonists. Formation of 2-deoxy[1-(14)C]-glucose-6-phosphate or (14)CO2 was measured. 2-Deoxy[1-(14)C]-glucose uptake and beta-adrenoceptor mRNA were measured in C2C12 cells. KEY RESULTS: 10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2-deoxyglucose uptake in soleus muscle by 33-54%. The effect of BRL37344 was prevented by 1 microM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 microM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 stimulated 2-deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only beta2-adrenoceptor mRNA could be detected by RT-PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2-deoxyglucose uptake and the effect of clenbuterol was not significant. CONCLUSIONS AND IMPLICATIONS: Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via beta2-adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2-deoxyglucose uptake.