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Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes

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Summary

Activities (μmol x min−1 x g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes.

  1. 1.

    Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and β-hydroxybutyrate being elevated by more than fivefold.

  2. 2.

    Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively.

  3. 3.

    The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocinand alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones.

  4. 4.

    The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected.

  5. 5.

    Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.

The results indicate that both in the ketotic and nonketotic diabetic state the gluconeogenic capacity of the liver was increased mainly in the periportal zone and the glycolytic capacity was decreased mainly in the perivenous area. In both types of diabetes the glucostat function of the liver with its typical reciprocal zonal distribution of glucogenic and glycolytic enzymes was not lost, but only impaired owing to shifts of the enzyme levels in the periportal and perivenous zone. This quantitative rather than qualitative alteration would be in accord with the requirement for the liver persisting in both non-ketotic and ketotic diabetes to handle excess nutritional glucose at least in part.

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  1. Institut für Biochemie, Fachbereich Medizin der Universität Göttingen, Humboldtallee 23, D-3400, Göttingen, Germany

    H. Miethke, B. Wittig, A. Nath & K. Jungermann

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  1. H. Miethke
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  2. B. Wittig
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  3. A. Nath
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  4. K. Jungermann
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Miethke, H., Wittig, B., Nath, A. et al. Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes. Histochemistry 85, 483–489 (1986). https://doi.org/10.1007/BF00508430

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