Liver, muscle, and adipose tissue are resistant to insulin action in type 2 diabetes. In spite of intensive studies, few diabetic genes have been identified. Recently, mitochondrial impairment has been observed in the muscle and adipose tissues of type 2 diabetes patients, implying that mitochondrial dysfunction could be a pivotal factor in type 2 diabetes. Here, we discuss mitochondrial malfunction leading to type 2 diabetes.
Adipose Tissue ; Humans ; Insulin ; Liver ; Mitochondria*

Liver, muscle, and adipose tissue are resistant to insulin action in type 2 diabetes. In spite of intensive studies, few diabetic genes have been identified. Recently, mitochondrial impairment has been observed in the muscle and adipose tissues of type 2 diabetes patients, implying that mitochondrial dysfunction could be a pivotal factor in type 2 diabetes. Here, we discuss mitochondrial malfunction leading to type 2 diabetes.
Adipose Tissue ; Humans ; Insulin ; Liver ; Mitochondria*

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.
Humans ; Liver/metabolism* ; Liver Diseases ; Autophagy ; Metabolic Diseases ; Mitochondria

Cadmium/metabolism* ; Kidney ; Cells, Cultured ; Mitochondria ; Metallothionein/metabolism* ; Liver

PURPOSE: This study was designed to investigate whether valproic acid(VPA) induces Reye's syndrome by analyzing blood chemistry, carnitine(CARN) concentration, and the morphologic changes of hepatocytes. The changes of GFAP immunoreactivity of astrocytes were examined in rats with Reye's syndrome induced by VPA. And the effects of CARN supplementation on Reye's syndrome were also investigated. METHODS: Ten rats were assigned to each of the following 3 groups : control group(0.5ml of normal saline), VPA group(250mg/kg of VPA), and VPA plus CARN group(250mg/kg of VPA and 100mg/kg of CARN). Each dose was injected intraperitoneally every 12 hours for 7 days. All rats fasted overnight following the final injection. RESULTS: In the VPA group, the levels of glucose and ketones decreased and the levels of ammonia, SGOT and lactates increased as compared with the control group. Lower levels of free CARN and higher acyl/free CARN ratios, indicating secondary CARN deficiency, were observed, and the appearance of transformed mitochondria of hepatocytes provided further evidence of mitochondrial metabolic dysfunction in Reye's syndrome. The GFAP immunoreactivity and the area percent of GFAP-positive astrocytes in the cingulum decreased in VPA group. In the VPA plus CARN group, there were no significant differences with the control group in blood chemistry, acyl/free CARN ratios and morphology of hepatocytes. However, the GFAP immunoreativity and the percent of GFAP-positive astrocytes in the cingulum decreased as much as in the VPA group. CONCLUSION: It is suggested that CARN supplementation may prevent abnormal findings of blood chemistry, CARN deficiency and the morphologic changes of liver mitochondria due to VPA, but CARN may have little effect on GFAP immunoreactivity of astrocytes in rats with Reye's syndrome induced by VPA.
Ammonia ; Animals ; Aspartate Aminotransferases ; Astrocytes* ; Carnitine* ; Chemistry ; Glucose ; Hepatocytes ; Ketones ; Lactates ; Mitochondria ; Mitochondria, Liver ; Rats* ; Reye Syndrome* ; Valproic Acid*

The effects of 7-ethyl-8-methylf1avin (7-Et) and 7-methyl-8-ethyl-flavin (8-Et) on rat hepatic monoamine oxidase (MAO), brain MAO activity and 5-hydroxytryptamine (5-HT or serotonin) in rat brain were investigated. In the study of hepatic MAO activity, kynur-amine a nonphysiological substrate for both A and B type MAO, was used for a spectro-photometric method, and [14C]-labeled amines were also used for a radiometric procedure for camparison with MAO activity determined by the spectrophotometric method. The rate of change in MAO activity of hepatic mitochondria from rats receiving Rb-def and 7-Et and 8-Et flavin showed the activity was severely reduced during 8 weeks. Rapid reduction of enzyme activity (50% in def-group, 35% in 7-Et group and 8% 8-Et flavin group) was observed at the end of 2 weeks. The enzyme activity lasted with slow decre-ment of enzyme level from 4 weeks to the end of 8 weeks as low as 16% in def, 18% in 7-Et and 3% in 8-Et flavin group. The trend of decrement of MAO activity when kynura-mine was used as a substrate appears to be similar with the small variation of MAO activity when [14C]-labelled tyramine, dopamine, serotonin and tryptamine respectively were used as substrate. The rate of decay of brain mitochondrial MAO activity in rats receiving each respective f1avin was not rapid and severely depressed as the MAO activity we have found in liver mitochondrial MAO of rats during the 8 week experimental time, but a similar tendency of decay of MAO in each group was observed. The potent inhibitory effect of 8-Et on brain MAO was confirmed by the study of the simultaneous measure-ment of MAO activity in each experimental group. when the reduction Of brain MAO activity in rats receiving 8-Et after 6 weeks was approximately 80% of normal and in the same rats the concentration of brain 5-HT showed a 60% increment of that of the normal mts. During the experimental period there is no absolute parallelism between the MAO inhibition and 5-HT increase. However when the reduction of MAO activity reached 80% of normal value, the concentration of 5-HT increased dramatically as much as 60% of normal value. The results so far suggest clearly that 8-Et produces a much more potent inhibitory effect on the hepatic MAO a s well as brain MAO in rats. Therefore our present and previous results suggest that 7-Et and 8-Et flavin should bind itself to hepatic, brain MAO apoenzyme in the condition of total absence of riboflavin in these animals, and the holenzyme is catalytically inactive.
Animal ; Brain/enzymology* ; Brain/metabolism ; Comparative Study ; Male ; Mitochondria/enzymology* ; Mitochondria, Liver/enzymology* ; Monoamine Oxidase/metabolism* ; Rats ; Serotonin/metabolism*

OBJECTIVEA study on the value of antimitochondrial antibody (AMA) and its subtypes anti-M2, anti-M4, and anti-M9 in diagnosing primary biliary cirrhosis (PBC).

METHODSAntimitochondrial antibody was detected by indirect immunofluorescence and anti-M2, anti-M4 and anti-M9 by Western blotting. AMA and anti-M2 of 78 PBC patients, of 35 non-PBC hepato-biliary disease patients and 20 healthy controls were studied and anti-M2, anti-M4 and anti-M9 were studied in 30 of the 78 PBC patients.

RESULTS96.2% (75/78) of PBC patients were AMA positive and 94.9% (74/78) of PBC patients were anti-M2 positive. Only three among the 35 non-PBC patients were positive for AMA (one with very low titre). None of the 35 non-PBC patients was anti-M2 positive. AMA and anti-M2 were negative in all the healthy controls. Among the 30 anti-M2 positive patients, 16 patients were anti-M4 positive (16/30, 53.3%) and 4 patients were anti-M9 positive (4/30, 13.3%).

CONCLUSIONAMA and its subtypes (special anti-M2) are important sero-immunological markers for the diagnosis of PBC.

Autoantibodies ; blood ; classification ; Female ; Humans ; Liver Cirrhosis, Biliary ; diagnosis ; immunology ; Male ; Mitochondria, Liver ; immunology

Animals ; Dietary Supplements ; Electron Transport ; Hypoxia ; Iron ; pharmacology ; Liver ; Mitochondria, Liver ; drug effects ; Rats

Animals ; Endoplasmic Reticulum ; metabolism ; Fatty Liver ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Non-alcoholic Fatty Liver Disease

We have investigated the effect of cholestasis on the hepatic thiosulfate sulfurtransferase (rhodanese) and UDP-glucuronosyltransferase (UDP-GT) activities in rats. Rhodanese activities in the liver cytosol, mitochondria and microsomal fractions as well as in the rat serum, and UDP-GT activity in the microsome have been investigated for a period of 42 days after common bile duct (CBD) ligation. The cytosolic rhodanese activity showed a significant decrease between the first through the 42nd day, and the mitochondrial activity showed a significant decrease between the 7th through the 42nd day after CBD ligation compared to the activities from the sham operated control, respectively. In the case of microsomal preparation, both rhodanese and UDP-GT also showed significant decrease in their activities after the ligation for the former enzyme between the 14th and the 42nd days, and for the latter enzyme between the third and 42nd days, respectively. On the other hand, the serum rhodanese activity increased markedly soon after the ligation, exhibiting the peak activity after 1 day of CBD ligation with about 4.6-fold increment. The activity subsequently decreased gradually reaching to the control level at the 42nd day post-ligation. Enzyme kinetic parameters of hepatic rhodanese and UDP-GT were analyzed using sodium thiosulfate and p-nitrophenol as substrates, respectively, with the preparations from the 28th day post-ligation. The results indicated that although the K-m values of these enzymes were about the same as the sham-operated control, the V-max values of the both enzymes decreased significantly. These results, therefore, suggest that the biosynthesis of rhodanese and UDP-GT have been reduced in response to cholestasis, and that the elevation of rhodanese activity in the serum is most likely due to leakage from the liver subsequent to CBD ligation.
Animals ; Cholestasis ; Common Bile Duct* ; Cytosol ; Hand ; Ligation* ; Liver* ; Microsomes ; Mitochondria ; Rats* ; Sodium ; Thiosulfate Sulfurtransferase*