The liver in human diabetes. Concentration of some induced enzymes

Abstract

Since glycogen overloading is one of the outstanding features of the diabetic liver, a series of investigations were undertaken to find an enzymatic explanation of this feature. Three groups of patients were studied: non diabetics submitted to liver biopsy during surgery (group A); non diabetics submitted to percutaneous liver biopsy (group B). In both these groups G-6-PDH, PK and MDH were assayed, all these being adaptive enzymes of intermediate metabolism. Results were expressed as muU/100 mg proteins. The significant finding of the comparison of these two groups was the low concentration of these enzymes in surgical biopsies. The depression was such that for G-6-PDH the concentration was more than 10 times less in surgical specimens as compared to percutaneous ones, whereas for PK it was almost 10 times less. In view of these findings no further surgically obtained biopsy material was used in this study. The third group (C) included insulin-dependent diabetics in good metabolic control from whom percutaneous liver biopsies were obtained for the assay of the same enzymes as above and in order to compare the results with those of group B. All three enzymes were diminished in diabetics, the difference being statistically significant for G-6-PDH and PK, not for MDH in view of the wide dispersion of the values found. Comparison and analysis of these results lead to the conclusion that in view of the low concentration of these enzymes in diabetics, glucose utilization in the liver cell must be presumed to be increased via other metabolic pathways.

Diabetic‑induced alterations in hepatic glucose and lipid metabolism: The role of type 1 and type 2 diabetes mellitus (Review)

“…In DM, previous findings have demonstrated that the activity of G6Pd is inhibited and the content of nadPH is reduced in the liver of T1dM rats (induced by STZ-and alloxan-treatment) (96). Similar findings have also been reported in the liver of patients with chronic dM (97). in an animal study of mild, moderate and severe hyperglycemia induced by STZ and nicotinamide treatment, it was found that the levels of hepatocyte glucose-6-phosphate dehydrogenase (G6Pd) activity in mild hyperglycemia remained similar to the normal values, whereas in moderate and severely hyperglycemia, they were significantly reduced (94).…”

Synergistic activation of glucose-6-phosphate dehydrogenase and NAD(P)H oxidase by Src kinase elevates superoxide in type 2 diabetic, Zucker fa/fa, rat liver

“…The fate of glucose through the PPP has not been well characterized and there is conflicting evidence about the activity of G6PD, the first/rate limiting enzyme in the PPP, in diabetes. For example, some studies suggest that G6PD activity is inhibited and NADPH is decreased in islets cells [26], Leydig cells [27], kidneys [28], lens [29], heart [30] and the liver [31] of type 1 diabetic rats (induced by streptozotocin- and alloxan-treatment); and in the liver [32], mononuclear leukocytes [33] and erythrocytes [34] of chronic diabetic patients. In contrast, recent studies have shown that G6PD is over-expressed in the adipocytes of obese (including db/db , ob/ob , and diet-induced obesity) mice, adipocytes and stromal-vascular cells of diabetic db/db mice, and adipocytes cultured, in vitro, under high glucose conditions [35, 36].…”

Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex

“…This observation is consistent with previously published data in which decreased G6PD activity has also been observed in liver (33), aorta (43), heart (27,42), and Leydig cells (5) from diabetic animal models. Moreover, it has been reported that patients with diabetes have decreased G6PD levels in liver (6), mononuclear leukocytes (34,44), and erythrocytes (9,10). Our data, along with many others (13,35,47), strongly suggest that decreased G6PD activity is of significance in the pathogenesis of diabetic complications.…”