The Effects of Insulin on Plasma Mevalonate Concentrations in Man

Abstract

Mevalonate production is a limiting step in cholesterol synthesis. We studied the effects of insulin on plasma mevalonate concentrations during a 3-hour euglycemic hyperinsulinemic clamp study in 10 healthy males starting at 9 h a.m. after 14 h of fasting. Physiological variations in plasma mevalonate were evaluated on a different day from 9 to 12 h a.m. under saline infusion. During the clamp studies, slight but significant decreases were noted for VLDL-triglyceride and VLDL-cholesterol at 120 and 180 min (p < 0.05) and for apolipoprotein B-100 from 60min on (p < 0.05). Plasma mevalonate decreased significantly by 34 and 41% at 120 and 180 min, respectively (p < 0.001), while the mean percent decrease due to diurnal variations was 12% at 12 h a.m. In conclusion, hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of mevalonic acid, the immediate product of HMG CoA reductase in the cholesterol pathway.

Effects of Insulin on Cholesterol Synthesis in Type II Diabetes Patients

“…To clarify further the effect of insulin on MVA, we also performed in our patients a 3-h hyperinsulinemic clamp study. Basal MVA values were in the normal range for our laboratory, and the slight decrease after saline infusion reflected the physiological fall throughout the morning related to the diurnal rhythm of this compound in normal subjects (17,27). The clear-cut reduction observed during the clamp studies confirms previous observations in normal subjects (27).…”

“…Basal MVA values were in the normal range for our laboratory, and the slight decrease after saline infusion reflected the physiological fall throughout the morning related to the diurnal rhythm of this compound in normal subjects (17,27). The clear-cut reduction observed during the clamp studies confirms previous observations in normal subjects (27). The decreased VLDL cholesterol concentrations may further support the hypothesis of a reduction of the hepatic cholesterol synthesis.…”

“…Plasma and urinary MVA concentrations correlate with cholesterol production rates in normal subjects (17,20,24) as well as in patients with different lipid disorders, namely, hypertriglyceridemia, homozygous and heterozygous familial hypercholesterolemia (17,18), abetalipoproteinemia, and homozygous hypobetalipoproteinemia (23). We have recently demonstrated that hyperinsulinemia in the presence of euglycemia acutely decreases MVA plasma concentrations in normal subjects (27).…”

Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers

“…The length of postprandial fasting can affect blood lipids in different ways: ®rstly, the exposition of liver to portal bile acids negatively affects the rate of cholesterol synthesis; secondly, prolonged fasting leads to higher levels of insulin release after the ®rst meal of the day, even more if the meal is large. It is known that insulin can stimulate cholesterol synthesis by activating the key enzyme of such a pathway, the HMG-CoA reductase (Lala et al, 1994). Increase in the meal frequency from 3 to 17 meals per day signi®cantly reduces serum total and LDL cholesterol, probably as a consequence of a reduced hepatic cholesterol synthesis related to the maintenance of low serum insulin levels in the nibbling diet (Jenkins et al, 1989).…”

Determination of Key Intermediates in Cholesterol and Bile Acid Biosynthesis by Stable Isotope Dilution Mass Spectrometry

“…insulin, growth hormone and thyroid hormone, on in vivo cholesterol metabolism. Euglycemic hyperinsulinemia acutely decreased the circulating levels of MVA (Lala et al 1994), which indicated that insulin could decrease cholesterol biosynthesis. Naoumova et al also investigated the effects of hyperinsulinemia on the plasma MVA concentrations and reported that acute hyperinsulinemia decreased cholesterol biosynthesis less in the subjects with non-insulin-dependent diabetes mellitus compared with non-diabetic subjects, which suggests that the patients with non-insulin-dependent diabetes mellitus exhibit insulin resistance (Naoumova et al 1996).…”