Cardioprotective effects of pectin-insulin patch in streptozotocin-induced diabetic rats

J Diabetes. 2017 Dec;9(12):1073-1081. doi: 10.1111/1753-0407.12538. Epub 2017 May 29.

Abstract

Background: Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus. Despite the beneficial effects of subcutaneous insulin, reports suggest that the therapy itself precipitates cardiovascular risks due to the high insulin concentration administered. It is therefore necessary to seek alternative routes of insulin administration that may bypass the undesirable effects associated with high plasma insulin concentrations. Accordingly, the present study investigated the effects of a novel transdermal pectin-insulin patch on selected markers of cardiovascular function in diabetes.

Methods: Pectin-insulin matrix patches (20.0, 40.8, and 82.9 μg/kg) were prepared as described previously. The three formulations were applied to streptozotocin-induced diabetic rats thrice daily. Blood glucose concentrations and mean arterial pressure (MAP) were monitored weekly for 5 weeks. Rats were then killed and blood collected for analysis of the lipid profile, cardiotropin-1, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP).

Results: The patches decreased blood glucose concentrations and diabetes-induced disturbances in lipid profile were attenuated by patch application (82.9 μg/kg). The diabetes-induced increase in MAP was also attenuated in patch (82.9 μg/kg)-treated rats. Patch treatment resulted in a decreased heart weight: body weight ratio, as well as reductions in cardiotropin-1, TNF-α, and hsCRP concentrations.

Conclusions: Application of the pectin-insulin patch protects against the debilitating cardiovascular effects associated with conventional diabetes treatment. This suggests that the pectin-insulin patch may provide an effective alternative therapeutic approach to the commonly used subcutaneous insulin injections in the management of diabetes.

Keywords: hyperglycemia; inflammation; lipid profile; mean arterial pressure; pectin-insulin patch; 平均动脉压; 果胶-胰岛素贴片; 炎症; 血脂谱; 高血糖.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Insulin / administration & dosage
  • Insulin / chemistry
  • Insulin / pharmacology*
  • Lipids / blood
  • Male
  • Pectins / chemistry*
  • Rats, Sprague-Dawley
  • Transdermal Patch
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Blood Glucose
  • Cardiotonic Agents
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Tumor Necrosis Factor-alpha
  • Pectins
  • C-Reactive Protein