pectins and Diabetic-Nephropathies

Renal damage and dysfunction is attributed to sustained hyperglycaemia in overt diabetes. Subcutaneous insulin injections are beneficial in delaying the progression of renal dysfunction and damage in diabetics. However, the current mode of administration is associated with severe undesirable effects. In this study, we evaluated the ameliorative effects of pectin-insulin dermal patches on renal dysfunction in diabetes.. Pectin-insulin patches (20.0, 40.8 and 82.9 µg/kg) were applied on the skin of streptozotocin-induced diabetic rats, thrice daily for 5 weeks. Blood glucose concentration, blood pressure and urine output volume were recorded on week 5 after which the animals were sacrificed after which the kidneys and plasma were collected. Kidney nephrin expression and urinary nephrin concentration, albumin excretion rate (AER), creatinine clearance (CC) and albumin creatinine ratio (ACR) were assessed.. Patch application resulted in reduced blood glucose concentration and blood pressure. Furthermore, pectin-insulin patch treatment resulted in increased kidney nephrin expression and reduced urinary nephrin concentration. AER, CC ACR were also reduced post patch application.. The application of pectin-insulin patch limited diabetes associated kidney damaged and improved kidney function. These observations suggest that pectin-insulin patches may ameliorate kidney dysfunction that is associated with chronic subcutaneous insulin administration.

Topics: Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Insulin; Membrane Proteins; Pectins; Rats; Streptozocin; Transdermal Patch

The tight glycemic control required to attenuate chronic complications in type 1 diabetes mellitus requires multiple daily injections of bolus insulin which cause hyperinsulinemic edema and hypertension due to Na(+) retention. Reports indicate that pectin insulin (PI)-containing dermal patches sustain controlled insulin release into the bloodstream of streptozotocin (STZ)-induced diabetic rats. This study investigated whether PI dermal patches can improve the impaired renal function in diabetes. PI patches were prepared by dissolving pectin/insulin in deionized water and solidified with CaCl(2). Short-term (five weeks) effects of thrice daily treatments with PI patches on renal function and urinary glucose outputs were assessed in diabetic animals. Blood and kidney samples were collected after five weeks for measurements of selected biochemical parameters. Blood was also collected for insulin measurement 6 h following treatments. The low plasma insulin concentrations exhibited by STZ-induced diabetic rats were elevated by the application of insulin-containing dermal patches to levels comparable with control non-diabetic rats. Untreated STZ-induced diabetic rats exhibited elevated urinary glucose, K(+) outputs and depressed urinary Na(+) outputs throughout the 5-week period. Treatment with PI dermal patches increased urinary Na(+) output and reduced urine flow, urinary glucose and K(+) excretion rates in weeks 4 and 5. PI dermal patches increased GFR of diabetic rats with concomitant reduction of plasma creatinine concentrations. Transdermal insulin treatment also decreased the renal expressions of GLUT1 and SGLT1 of STZ-induced diabetic rats. We conclude that PI dermal patches deliver physiologically relevant amounts of insulin that can improve kidney function in diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Drug Monitoring; Glucose; Hypoglycemic Agents; Insulin; Kidney Function Tests; Pectins; Rats; Sodium-Glucose Transporter 1; Streptozocin; Transdermal Patch; Treatment Outcome