Regulation of the diurnal rhythm of rat liver β-hydroxy-β-methylglutaryl coenzyme A reductase activity by insulin, glucagon, cyclic AMP and hydrocortisone

Nepokroeff, Carl M.; Lakshmanan, M.; Ness, Gene C.; Dugan, Richard E.; Porter, John W.

doi:10.1016/0003-9861(74)90412-3

Cited by 167 publications

(35 citation statements)

References 25 publications

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“…34 Insulin treatment of persons with non-insulindependent diabetes significantly raised the cholesterol saturation index. 35 A higher insulin concentration could predispose to gallstone formation by increasing the activity of hydroxymethylglutaryl coenzyme A reductase, 36 the rate limiting enzyme in hepatic synthesis of new cholesterol, or by activating low density lipoprotein receptors 37 resulting in greater hepatic uptake of low density lipoprotein cholesterol. By inhibiting basal and cholecystokinin-stimulated gallbladder motility, insulin might also increase gallstone risk through an effect on motility.…”

Section: Discussionmentioning

confidence: 99%

Association of diabetes, serum insulin, and c-peptide with gallbladder disease

2000

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An inconsistent association has been found between gallbladder disease and diabetes mellitus. We hypothesized that insulin resistance rather than diabetes status may be a primary factor involved in gallstone formation. A total of 5,653 adult participants in the third United States National Health and Nutrition Examination Survey without known diabetes underwent gallbladder ultrasonography and phlebotomy after an overnight fast for measurement of serum insulin, C-peptide, and glucose. Gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. Subjects were characterized as having normal fasting glucose (F110 mg/dL), impaired fasting glucose (110 to F126 mg/dL), or undiagnosed diabetes (H126 mg/dL). After controlling for other known gallbladder disease risk factors, among women, undiagnosed diabetes was associated with increased risk of gallbladder disease (prevalence ratio [PR] ‫؍‬ 1.91, 95% confidence interval [CI] ‫؍‬ 1.29-2.83); whereas impaired fasting glucose was unassociated. Gallbladder disease risk in women increased with levels of fasting insulin (PR ‫؍‬ 1.63, 95% CI ‫؍‬ 1.11-2.40) and C-peptide (PR ‫؍‬ 2.07, 95% CI ‫؍‬ 1.32-3.25) comparing highest to lowest quintiles. However, the association of gallbladder disease with undiagnosed diabetes was not diminished when the model included fasting insulin (PR ‫؍‬ 1.85, 95% CI ‫؍‬ 1.24-2.77). In men, there was a statistically nonsignificant association with undiagnosed diabetes (PR ‫؍‬ 2.11, 95% CI ‫؍‬ 0.76-5.85), but no association of gallbladder disease with insulin or C-peptide. Among women higher fasting serum insulin levels increased the risk of gallbladder disease, but did not account for the increased risk in persons with diabetes. (HEPATOLOGY 2000;31:299-303.)

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Section: Discussionmentioning

confidence: 99%

Association of diabetes, serum insulin, and c-peptide with gallbladder disease

2000

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“…Insulin increases the activity of HMG-CoA reductase, the rate-limiting enzyme for cholesterol synthesis in the liver. 22,23 Insulin also activates low-density lipoprotein (LDL) receptors in the liver, and thereby increasing cholesterol excretion in the bile. 24 In fact, hyperinsulinaemia has been shown to be associated with increased risk of gallstones in several studies.…”

Section: Heaton Et Almentioning

confidence: 99%

Gallstone disease risk in relation to body mass index and waist-to-hip ratio in Japanese men

et al. 1999

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OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese men. DESIGN: Cross-sectional study. SUBJECTS: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the consecutive series of 7637 men aged 48 ± 59 y receiving a preretirement health examination at four hospitals of the Japan Self-Defense Forces between 1986 and 1994. MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central obesity. Analysis of the WHR was limited to a subset of data for the period 1991 ± 1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410). RESULTS: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose tolerance, BMI was signi®cantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a signi®cant positive association with each of the two conditions. When BMI and WHR were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones and postcholecystectomy. CONCLUSION: These ®ndings indicate that obesity is associated with increased gallstone risk in men.

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“…Portacaval shunting has also been demonstrated to cause increases in serum glucagon concentration [26,30,31]. Glucagon in pharmacologic [27] or physiologic [37] doses has been shown to decrease hepatic cholesterol synthesis possibly via an increase in hepatic cyclic adenosine 3′,5′-monophosphate (cyclic AMP). We therefore also measured serum glucagon and hepatic cyclic AMP changes following portal diversion in an attempt to correlate them with cholesterol synthesis rates.…”

Section: Discussionmentioning

confidence: 99%

The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

Francavilla

Jones

Benichou

et al. 1980

Journal of Surgical Research

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Hepatic cholesterol synthesis, hepatic cyclic AMP, and portal and peripheral insulin and glucagon levels were investigated in nine dogs and three baboons after complete portacaval shunt. Cholesterol synthesis as measured with acetate incorporation was reduced in both species. Hepatic cyclic AMP increased in dogs. Changes in portal and systemic insulin were inconsistent, but hyper-glucagonemia occurred regularly. Diminished hepatic cholesterol synthesis is apparently one factor, although probably not the only one, in the antilipidemic effect of portacaval shunt. This altered cholesterol metabolism may be due to a change in the hormonal environment of the liver caused by portal diversion.

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Regulation of the diurnal rhythm of rat liver β-hydroxy-β-methylglutaryl coenzyme A reductase activity by insulin, glucagon, cyclic AMP and hydrocortisone

Cited by 167 publications

References 25 publications

Association of diabetes, serum insulin, and c-peptide with gallbladder disease

Association of diabetes, serum insulin, and c-peptide with gallbladder disease

Gallstone disease risk in relation to body mass index and waist-to-hip ratio in Japanese men

The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

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