Adverse Metabolic Effects of Diltiazem Treatment During Diabetic Cardiomyopathy
Autor: | Matt Parriman, Allison Campolo, Amanda Waller, Véronique A. Lacombe |
---|---|
Rok vydání: | 2018 |
Předmět: |
Blood Glucose
Male medicine.medical_specialty Heart disease Diabetic Cardiomyopathies medicine.drug_class Calcium channel blocker 030204 cardiovascular system & hematology Diltiazem Random Allocation 03 medical and health sciences 0302 clinical medicine Internal medicine Diabetes mellitus Diabetic cardiomyopathy medicine Animals Homeostasis Pharmacology (medical) Epidemic disease 030212 general & internal medicine Rats Wistar Muscle Skeletal Pharmacology business.industry Glucose transporter Calcium Channel Blockers medicine.disease Rats Disease Models Animal Metabolic effects Cardiology Cardiology and Cardiovascular Medicine business medicine.drug |
Zdroj: | Journal of Cardiovascular Pharmacology and Therapeutics. 24:193-203 |
ISSN: | 1940-4034 1074-2484 |
Popis: | Diabetes is a global epidemic disease, which leads to multiorgan dysfunction, including heart disease. Diabetes results from the limited absorption of glucose into insulin-sensitive tissues. The heart is one of the main organs to utilize glucose as an energy substrate. Glucose uptake into striated muscle is regulated by a family of membrane proteins called glucose transporters (GLUTs). Although calcium channel blockers, including diltiazem, are widely prescribed drugs for cardiovascular diseases, including in patients with diabetes, their pharmacological effects on glucose metabolism are somewhat controversial. We hypothesized that diltiazem treatment will exhibit detrimental effects on whole body glucose homeostasis and glucose transport in the striated muscle of patients with diabetes. Healthy and streptozotocin-treated rats were randomly assigned to receive diltiazem treatment or a placebo for 8 weeks. Blood glucose was significantly increased in the untreated diabetic groups, which worsened after diltiazem treatment. Diabetes decreased protein content of both GLUT4 (the predominate insulin-sensitive glucose transporter) and AS160 (Akt Substrate at 160 kDa, the downstream protein in the signaling cascade that regulates GLUT4 trafficking) in striated muscle of diabetic rats, with a more pronounced alteration after diltiazem treatment. We additionally reported that diabetic rodents displayed marked systolic dysfunction, which was not rescued by diltiazem treatment. In conclusion, diltiazem treatment worsened the effects of diabetes-induced hyperglycemia and diabetes-induced alterations in the regulation of glucose transport in striated muscle. |
Databáze: | OpenAIRE |
Externí odkaz: |