Insulin-Mediated Glucose Metabolism Is Related to Liver Structure and Microsomal Function

Lahtela, Jorma; Arranto, Arno J.; Stenbäck, Frej; Sotaniemi, Eero A.

doi:10.3109/00365528609011110

Cited by 4 publications

(3 citation statements)

References 21 publications

(8 reference statements)

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“…A decrease in plasma glucose and an improvement in sensitivity to insulin have been shown in diabetic patients after chronic phenobarbital treatment (Lathela et al, 1984(Lathela et al, , 1985(Lathela et al, , 1986. Such a fall in plasma glucose after chronic phenobarbital treatment may be due to a decrease in the glucogenic rate, since excessive hepatic glucose production is one of the major features in diabetic patients (Best et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital

Argaud

Halimi

Catelloni

et al. 1991

Biochemical Journal

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Gluconeogenesis was studied in hepatocytes isolated from phenobarbital-pretreated rats fasted for 24 h. In closed vial incubations, glucose production from lactate (20 mmol/l) and pyruvate (2 mmol/l), alanine (20 mmol/l) or glutamine (20 mmol/l) was suppressed by about 30-45%, although glycerol metabolism was not affected. In hepatocytes perifused with lactate and pyruvate (ratio 10:1), glucose production was inhibited by 50%, even at low gluconeogenic flux. From the determination of gluconeogenic intermediates at several steady states of gluconeogenic flux, we have found a single relationship between phosphoenolpyruvate and the rate of glucose production (Jglucose), and two different curves between cytosolic oxaloacetate and Jglucose in controls and in phenobarbital-pretreated hepatocytes. By using 3-mercaptopicolinate to determine the flux control coefficient of phosphoenolpyruvate carboxykinase we found that phenobarbital pretreatment led to an increase in this coefficient from 0.3 (controls) to 0.8 (phenobarbital group). These observations were confirmed by the finding that the activity of phosphoenolpyruvate carboxykinase was decreased by 50% after phenobarbital treatment. Hence we conclude that the inhibitory effect of phenobarbital on gluconeogenesis is due, at least partly, to a decrease in the flux through phosphoenolpyruvate carboxykinase.

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Section: Introductionmentioning

confidence: 99%

Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital

Argaud

Halimi

Catelloni

et al. 1991

Biochemical Journal

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“…Metabolic perturbations can lead to spill-over of extra free FAs from adipose tissue and their entry to liver and other organs via the activated adipose triglyceride lipase and hormone-sensitive lipase (53), induce hepatic fatty regeneration and cholestasis, and worsen the underlying causes of liver injury, such as diabetes–obesity-related liver disease (22,51). Both plasma lipoprotein risk factor levels (18,54) and glucose disposal rate (55) vary in proportion to the amount of unaltered parenchyma in diseased liver as evaluated by morphometry.…”

Section: Er Stress In Clinical Disorders and Diseasesmentioning

confidence: 99%

Elimination of endoplasmic reticulum stress and cardiovascular, type 2 diabetic, and other metabolic diseases

Luoma

2012

Annals of Medicine

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Multiple factors including unhealthy living habits influence the life-maintaining functions of the endoplasmic reticulum (ER) and induce ER stress and metabolic abnormalities. The ER responds to the disturbances by activating mechanisms that increase the capacity to eliminate ER stress. This article elucidates the effects of ER activation that eliminates both ER stress and associated cardiovascular, type 2 diabetic (DM2), and other metabolic diseases. ER-activating compounds eliminate ER stress by lowering elevated cholesterol, regress atherosclerosis, decrease cardiovascular mortality, reduce blood glucose and insulin, and, together with the normalization of glucose–insulin homeostasis, remove insulin resistance, pancreatic β-cell failure, and DM2. A deficient cytochrome P450 activity in hepatic ER leads to cholesterol accumulation that induces stress and xanthoma formation, whereas P450-activating therapy up-regulates apolipoprotein AI and LDLR genes, down-regulates apolipoprotein B gene, and produces an antiatherogenic plasma lipoprotein profile. The ER activation reduces the stress also by eliminating hepatic fat and converting saturated fatty acids (FAs) to unsaturated FAs. Cognitive processes require gene expression modification, and preclinical studies indicate that ER-activating therapy improves cognition. Promotion of healthy lifestyle choices and indicated therapies are key factors in the prevention and elimination of ER stress and associated global health problems.

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“…In subjects with liver disease glucose disposal rate varies proportionately to the amount of unaltered hepatic parenchyma as evaluated morphometrically, and to hepatic P450-mediated AP kinetics [54]. The glucose disposal rate was lowest among patients with fatty liver and those with liver cirrhosis.…”

Section: Effects Of Gene-activators On Liver Er and Glucose And Insulinmentioning

confidence: 99%

Gene-Activation Mechanisms in the Regression of Atherosclerosis, Elimination of Diabetes Type 2, and Prevention of Dementia

2011

CMM

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Atherosclerotic vascular disease, diabetes mellitus (DM) and dementia are major global health problems. Both endogenous and exogenous factors activate genes functioning in biological processes. This review article focuses on gene-activation mechanisms that regress atherosclerosis, eliminate DM type 2 (DM2), and prevent cognitive decline and dementia. Gene-activating compounds upregulating functions of liver endoplasmic reticulum (ER) and affecting lipid and protein metabolism, increase ER size through membrane synthesis, and produce an antiatherogenic plasma lipoprotein profile. Numerous gene-activators regress atherosclerosis and reduce the occurrence of atherosclerotic disease. The gene-activators increase glucose disposal rate and insulin sensitivity and, by restoring normal glucose and insulin levels, remove metabolic syndrome and DM2. Patients with DM2 show an improvement of plasma lipoprotein profile and glucose tolerance together with increase in liver phospholipid (PL) and cytochrome (CYP) P450. The gene-activating compounds induce hepatic protein and PL synthesis, and upregulate enzymes including CYPs and glucokinase, nuclear receptors, apolipoproteins and ABC (ATP-binding cassette) transporters. They induce reparation of ER structures and eliminate consequences of ER stress. Healthy living habits activate mechanisms that maintain high levels of HDL and apolipoprotein AI, promote health, and prevent cognitive decline and dementia. Agonists of liver X receptor (LXR) reduce amyloid in brain plaques and improve cognitive performance in mouse models of Alzheimer`s disease. The gene activation increases the capacity to withstand cellular stress and to repair cellular damage and increases life span. Life free of major health problems and in good cognitive health promotes well-being and living a long and active life.

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Insulin-Mediated Glucose Metabolism Is Related to Liver Structure and Microsomal Function

Cited by 4 publications

References 21 publications

Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital

Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital

Elimination of endoplasmic reticulum stress and cardiovascular, type 2 diabetic, and other metabolic diseases

Gene-Activation Mechanisms in the Regression of Atherosclerosis, Elimination of Diabetes Type 2, and Prevention of Dementia

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