Abstract
Carnitine insufficiency is reported in type 1 diabetes mellitus. To determine whether this is accompanied by defects in biosynthesis and/or renal uptake, liver and kidney were obtained from male Sprague-Dawley rats with streptozotocin-induced diabetes. Diabetic rats exhibited the metabolic consequences of type 1 diabetes, including hypoinsulinemia, hyperglycemia, and increased urine output. Systemic hypocarnitinemia, expressed as free carnitine levels, was evident in the plasma, liver, and kidney of diabetic rats. Compared to control rats, the low free carnitine in the plasma of diabetic rats was accompanied by decreased expression of γ-butyrobetaine hydroxylase in liver and kidney, suggesting impaired carnitine biosynthesis. Expression of organic cation transporter-2 in kidney was also reduced, indicating impaired renal reabsorption, and confirmed by the presence of elevated levels of free carnitine in the urine of diabetic rats. Insulin treatment of diabetic rats reversed the plasma hypocarnitinemia, increased the free carnitine content in both kidney and liver, and prevented urinary losses of free carnitine. This was associated with increased expression of γ-butyrobetaine hydroxylase and organic cation transporter-2. The results of our study indicate that type 1 diabetes induced with streptozotocin disrupts carnitine biosynthesis and renal uptake mechanisms, leading to carnitine insufficiency. These aberrations in carnitine homeostasis are prevented with daily insulin treatment.
Highlights
Carnitine is essential in the transfer of long-chain fatty acids (FAs) across mitochondrial membranes where they undergo β-oxidation for energy production [1]
We examined the effects of STZ-induced diabetes and insulin treatment on γ-butyrobetaine hydroxylase (γ-BBH) and OCTN2 expression in liver and kidney as well as on free carnitine (FC) levels in plasma, urine, and tissues in diabetic rats
We we propose pose that insulinopenia decreases protein expression of γ-BBH and OCTN2 in liver and kidney, that insulinopenia decreases protein expression of γ-BBH and OCTN2 in liver and kidney, resulting resulting in impaired biosynthesis and increased excretion of FC
Summary
Carnitine is essential in the transfer of long-chain fatty acids (FAs) across mitochondrial membranes where they undergo β-oxidation for energy production [1]. In addition to this critical role, carnitine acts as buffer of the CoA pool, excretes potentially toxic acylCoA residues from cells, and regulates the intramitochondrial ratio of acetyl CoA to. The liver and kidneys are the main sites for carnitine biosynthesis because all other tissues lack considerable γ-BBH activity [10]. Tissues lacking γ-BBH activity release BB into circulation for subsequent uptake by the liver and kidneys, where this precursor is converted to carnitine [11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
