title: The effects of transdermal insulin treatment of streptozotocin-induced diabetic rats on kidney function and renal expression of glucose transporters.
abstract: 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.
authors.affiliation: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.
authors.forename: Phikelelani Siphosethu
authors.initials: PS
authors.lastname: Ngubane
authors.forename: Silindile Innocentia
authors.initials: SI
authors.lastname: Hadebe
authors.forename: Metse Regina
authors.initials: MR
authors.lastname: Serumula
authors.forename: Cephas T
authors.initials: CT
authors.lastname: Musabayane
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy; D016903:Drug Monitoring; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007677:Kidney Function Tests / Q000379:methods; D010368:Pectins / Q000494:pharmacology; D051381:Rats; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D051269:Sodium-Glucose Transporter 1; D013311:Streptozocin; D010368:Pectins; D005947:Glucose
keywords: Diabetes; GLUT1; SGLT1; hyperglycemia; insulin; kidney function; pectin; transdermal