Antidiabetic activity of aqueous stem bark extract of Annickia polycarpa in alloxan-induced diabetic mice.

BACKGROUND AND AIM: There is a growing need to develop new drugs for type II diabetes mellitus (DM) from plant sources due to the high cost and adverse side effects of current drug therapies. To this end, the antidiabetic activity of aqueous stem-bark extract of A. polycarpa (APE) in alloxan-induced diabetic ICR mice was investigated. EXPERIMENTAL PROCEDURE: The effect of APE (20, 100 and 500 mg/kg), glibenclamide and metformin as positive controls, were determined over 4 weeks on fasting blood glucose (FBG). An oral glucose tolerance test (OGTT) was also conducted. The effects of these treatments on the morphology of the pancreas were assessed. In addition, phytochemical constituents and antioxidant properties of APE were determined. RESULTS AND CONCLUSION: APE, like glibenclamide and metformin, showed significant hypoglycaemic effect. The OGTT supported the hypoglycaemic effect. The destroyed pancreatic beta-cells in diabetic control mice were restored to normal by APE or drug treatment. APE showed antioxidant activity by scavenging DPPH free radicals; this may be due to the presence of phenolic compounds, particularly flavonoids. Thus, APE may act by restoring pancreatic beta-cell integrity through mopping of reactive oxygen species (ROS) associated with the diabetic state, and thereby improving pancreatic function and consequently, the lowering of FBG levels. These findings provide ample evidence to validate the traditional use of A. polycarpa in the management of DM.

Tobacco smoking is associated with decreased semen quality.

BACKGROUND: Tobacco smoking is a public health issue and has been implicated in adverse reproductive outcomes including semen quality. Available data however provides conflicting findings. The objective of this study was to evaluate the effect of tobacco smoking on semen quality among men in Ghana. METHODS: In this study, a total of 140 subjects were recruited, comprising 95 smokers and 45 non-smokers. Smokers were further categorized into mild, moderate and heavy smokers. Semen parameters such as sperm concentration, motility, viability and normal morphology were measured according to the World Health Organisation criteria. RESULTS: The study showed that smokers had significantly lower semen volume, sperm concentration, sperm motility, total sperm count, sperm morphology, free testosterone and follicle stimulating hormone (p <0.05 respectively), compared with non-smokers. Smokers were at a higher risk of developing oligospermia, asthenozoospermia and teratozoospermia (OR = 3.1, 4.2 and, 4.7; p <0.05) than non-smokers. CONCLUSION: Results demonstrated a decline in semen quality in a dose dependent tobacco smoking manner.

Relationship between oxidative stress and haematological indices in patients with diabetes in the Ghanaian population.

BACKGROUND: Persistent hyperglycaemia is a hallmark of Diabetes Mellitus (DM). It causes increased production of free radicals, especially reactive oxygen species (ROS), - resulting in oxidative stress. Reactive Oxygen Species have been implicated in the development of haematological complications in patients with diabetes. Superoxide Dismutase (SOD) is one of the most effective antioxidant enzyme defense systems against free radicals. METHODS: From February through May 2014, we assessed the relationship between oxidative stress and haematological profiles among individuals with and without diabetes. A cross sectional study of 66 case patients and 44 age-matched controls were recruited from the National Diabetes Management and Research Centre (NDMRC), Korle-Bu Teaching Hospital, Accra, Ghana. Blood samples were obtained from study participants with consent. We determined the haematological profiles of study participants and measured their oxidative stress levels using a standardized kit for SOD activity. RESULTS: Higher white blood cell (WBC) counts were seen in the diabetes cohort (p-value = 0.023). The SOD activity tended to be lower in diabetes patients (p-value = 0.144 however) while higher neutrophil levels seemed to correlate with SOD activity (R = 0.249; R2 = 6.2 %; p-value = 0.049). There did not appear to be a correlation between fasting blood glucose (FBG) and SOD activity (R = -0.044; p-value = 0.727). CONCLUSION: The study reports similar oxidative stress levels, as measured by SOD activity, in diabetic and non-diabetic adults. The SOD activity did not appear to correlate with FBG and several other haematological parameters. Further study would be required to investigate the relationship between these haematological indices and diabetic micro- and macro-vascular complications in our population.

A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro.

Many plant-based products have been suggested as potential antidiabetic agents, but few have been shown to be effective in treating the symptoms of Type 2 diabetes mellitus (T2DM) in human studies, and little is known of their mechanisms of action. Extracts of Gymnema sylvestre (GS) have been used for the treatment of T2DM in India for centuries. The effects of a novel high molecular weight GS extract, Om Santal Adivasi, (OSA(R)) on plasma insulin, C-peptide and glucose in a small cohort of patients with T2DM are reported here. Oral administration of OSA(R) (1 g/day, 60 days) induced significant increases in circulating insulin and C-peptide, which were associated with significant reductions in fasting and post-prandial blood glucose. In vitro measurements using isolated human islets of Langerhans demonstrated direct stimulatory effects of OSA(R) on insulin secretion from human ß-cells, consistent with an in vivo mode of action through enhancing insulin secretion. These in vivo and in vitro observations suggest that OSA(R) may provide a potential alternative therapy for the hyperglycemia associated with T2DM.

Human islets derived from donors after cardiac death are fully biofunctional.

Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heart-beating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets from BDDs over the same time period. The quantity and quality of islets from NHBDs was good. NHBD yielded approximately 12.6% more islets than those of BDDs (505,000 +/- 84,230 vs. 400,970 +/- 172,430 islet equivalent number [IEQ]/pancreas, p = 0.01) with comparable viability. ATP and GTP contents were lower (6.026 +/- 3.076 vs. 18.105 +/- 7.8 nM/mg protein, p = 0.01 and 1.52 +/- 0.87 vs. 3.378 +/- 0.83 nM/mg protein, p = 0.04) and correlated negatively to warm ischemia time (R(2)= 0.8022 and R(2)= 0.7996, respectively). Islets from NHBDs took longer to control hyperglycemia in diabetic mice, but were equally able to sustain euglycemia. With a warm ischemia time (WIT) of

Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice.

AIMS/HYPOTHESIS: Insulin signalling pathways regulate pancreatic beta cell function. Conditional gene targeting using the Cre/loxP system has demonstrated that mice lacking insulin receptor substrate 2 (IRS2) in the beta cell have reduced beta cell mass. However, these studies have been complicated by hypothalamic deletion when the RIPCre (B6.Cg-tg(Ins2-cre)25Mgn/J) transgenic mouse (expressing Cre recombinase under the control of the rat insulin II promoter) is used to delete floxed alleles in insulin-expressing cells. These features have led to marked insulin resistance making the beta cell-autonomous role of IRS2 difficult to determine. To establish the effect of deleting Irs2 only in the pancreas, we generated PIrs2KO mice in which Cre recombinase expression was driven by the promoter of the pancreatic and duodenal homeobox factor 1 (Pdx1, also known as Ipf1) gene. MATERIALS AND METHODS: In vivo glucose homeostasis was examined in PIrs2KO mice using glucose tolerance and glucose-stimulated insulin secretion tests. Endocrine cell mass was determined by morphometric analysis. Islet function was examined in static cultures and by performing calcium imaging in Fluo3am-loaded beta cells. Islet gene expression was determined by RT-PCR. RESULTS: The PIrs2KO mice displayed glucose intolerance and impaired glucose-stimulated insulin secretion in vivo. Pancreatic insulin and glucagon content and beta and alpha cell mass were reduced. Glucose-stimulated insulin secretion and calcium mobilisation were attenuated in PIrs2KO islets. Expression of the Glut2 gene (also known as Slc2a2) was also reduced in PIrs2KO mice. CONCLUSIONS/INTERPRETATION: These studies suggest that IRS2-dependent signalling in pancreatic islets is required not only for the maintenance of normal beta and alpha cell mass but is also involved in the regulation of insulin secretion.

Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells.

Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus.