We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.
Previous studies in our laboratories suggest that oral administration of some herbal extracts reduce blood glucose concentrations in rats, possibly by interfering with food consumption and/or gastrointestinal absorption of food. Accordingly, we monitored the amounts of food consumed and body weights in separate groups of nondiabetic and streptozotocin-treated diabetic rats, orally treated with some plant extracts (20 mg 100 g -1 body weight) daily for 5 weeks. Control animals were administered the vehicle, citrate buffer (0.1 ml 100 g -1 body weight). Separate groups of rats administered allopathic hypoglycemic drugs metformin (50 mg 100 g -1 body weight) or glibenclamide (5 microg 100 g -1 body weight) acted as positive control animals. After 5 weeks, blood glucose concentrations were reduced in all the groups. Tapinanthus nyasicus leaf, Ficus thoningii bark, Solanum incanum fruit, and Morus alba leaf extracts decreased weekly food consumption throughout the 5-week study period. Similar results were obtained for the groups treated with metformin or glibenclamide. However, food consumption was increased by S. incanum root, Aloe chabaudii leaf, or Allium sativum bulb extracts, and this was associated with high prevalence of diarrhea. The herbal extracts and metformin did not affect serum insulin concentration in nondiabetic rats, while glibenclamide increased serum insulin concentration. In conclusion, it may be inferred that the herbal extracts examined produced hypoglycemia, probably by interfering with either food intake or gastrointestinal glucose absorption (as reported for metformin). These findings merit long-term investigation.
Diabetes is a risk factor for cardiovascular diseases (CVDs) and there are reports of increasing prevalence of prediabetes in Nigeria. This study therefore characterised CVDs risk factors in subjects with impaired fasting glucose (IFG) and diabetes. Data from 4 population-based cross-sectional studies on 2447 apparently healthy individuals from 18 - 89 years were analysed. Anthropometric, blood pressure and biochemical parameters were collected and classified. Individuals with IFG (prediabetes) and diabetes were merged each for positive cases of dyslipidaemia, high blood pressure (HBP) or obesity. Optimal Discriminant and Hierarchical Optimal Classification Tree Analysis (HO-CTA) were employed. Overall prevalence of IFG and diabetes were 5.8% (CI: 4.9 – 6.7%) and 3.1% (CI: 2.4 – 3.8%), respectively. IFG co-morbidity with dyslipidaemia (5.0%; CI: 4.1 – 5.8%) was the highest followed by overweight/obese (3.1%; CI: 2.5 – 3.8%) and HBP (1.8%; CI: 1.3 – 2.4%). The predicted age of IFG or diabetes and their co-morbidity with other CVD risk factors were between 40 – 45 years. Elevated blood level of total cholesterol was the most predictive co-morbid risk factor among IFG and diabetes subjects. Hypertriglyceridaemia was an important risk factor among IFG-normocholesterolaemic-overweight/obese individuals. The higher prevalence of co-morbidity of CVD risk factors with IFG than in diabetes plus the similar age of co-morbidity between IFG and diabetes highlights the need for risk assessment models for prediabetes and education of individuals at risk about factors that mitigate development of diabetes and CVDs.