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.

The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in P. berghei-Infected Male Sprague-Dawley Rats

“…This data demonstrates the ability of the OA-pectin patch to deliver sustained controlled therapeutic doses of OA which reduced and cleared the malaria parasites within a period of 4 days. Indeed, we have previously reported on the ability of transdermal systems to deliver drugs in a sustained controlled manner [23–30]. Similar to CHQ, both transdermal and orally administered OA were able to reduce parasitaemia to undetectable levels.…”

“…Studies have shown that these triterpenes are of low solubility when administered orally, which ultimately affects their bioavailability [20–21]. We have reported on the ability of transdermal CHQ and insulin matrix-pectin patch to provide sustained controlled release of CHQ and insulin over a period of time, respectively [22–24]. Against this background, the current study evaluated the effects of transdermally delivered OA and CHQ-OA combination on P .…”

Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

“…Most of the studies for GLUT1 evaluation in these models were carried out in streptozotocin (STZ) rats. They predominantly reported higher GLUT1 protein [79][80][81][82] and corresponding mRNA [81][82][83][84][85] contents in the whole kidney and increased GLUT1 protein [86,87] and mRNA [86,88,89] in the cortex. Nonetheless, these studies are yet controversial [22,67,[90][91][92][93].…”

The Ameliorative Effect of Pectin-Insulin Patch On Renal Injury in Streptozotocin-Induced Diabetic Rats

“…Non-diabetic animals served as the absolute control. Two days prior to the application of the pectin-insulin patches, the rats were shaved on the dorsal region of the neck [14]. The pectin-insulin patches were applied thrice daily, 8 hours apart for 5 weeks.…”

“…In our laboratory, we have successfully developed a transdermal pectin-insulin patch formulation that can deliver physiologically relevant insulin concentration which can maintain normal glycaemic control and ameliorate certain diabetes associated complications in streptozotocin (STZ) induced-diabetic rats [13, 14]. Accordingly, in the study, we sought to evaluate the effects of transdermal pectin-insulin patch application on markers of kidney function such as blood pressure, creatinine clearance, albumin excretion rate, kidney nephrin expression and urinary nephrin concentration.…”