HMGCR and metabolic syndrome: Insulin deficiency may be responsible for dyslipidemia, because insulin has an inhibitory action on HMG-CoA reductase, a key enzyme that is rate limiting in the metabolism of cholesterol rich LDL particles.[25] The mechanisms responsible for the development of hypertriglyceridemia in uncontrolled diabetes in humans (possibly in insulin deficient STZ-diabetic rats) may be due to a number of metabolic abnormalities that occur sequentially.