The effect of hydrocortisone phosphate, methylprednisolone and phenytoin on pancreatic insulin release and hepatic glutathione-insulin transhydrogenase activity in the rat

Insulin Metabolism and Degradation*

“…Insulindeficient animals have decreased activity, whereas insulin treatment restores this activity (74)(75)(76)(77)(78)(79), apparently by an increase in enzyme synthesis (80). This finding has been interpreted as possibly reflecting a protective mechanism whereby in the presence of low levels of insulin less of the hormone is degraded, and this, therefore, provides more active hormone for the deficient cell.…”

Insulin degradation. XXVIII. Immunocytochemical localization of glutathione-insulin transhydrogenase in the pancreas, kidney and liver of normal and streptozotocin-diabetic rats and of lean and obese (ob/ob) mice

“…These apparent discrepancies in the biochemical data can now be reconciled on the basis of information provided by the current studies. Studies using liver homogenates yield average values whereas studies using isolated perfused intact liver indicate the function of a specific hepatic region [5], since the occurrence of GIT-rich and GIT-poor regions in tissues probably results in different net effective activities in different cellular compartments or local regions. Thus, while circulating insulin may represent a major control mechanism over GIT concentration, the occurrence of variable local concentrations of GIT might provide, as previously proposed [25], a mechanism by which the enzyme regulates the cleavage and/or the formation of disulphide bonds in proteins, depending upon the substrate [31], tissue and/or metabolic state of the cell.…”

“…Work using several models (normal, starved, starved-refed, alloxan-diabetic, streptozotocin-diabetic rats; obese and lean mice) has shown that the concentration of liver enzyme is under feedback control by the circulating level of insulin [5,16,17,18,23,30,32]. Several factors (mono-, di and protein thiols [4] glucagon and growth hormone [31], adrenalectomy Ill], glucocorticoids [5] and certain phospholipids [28]) have been found to modulate the activity of GIT [24 for a review]. In addition to regulation by these biochemical compounds, several different lines of evidence are suggestive that cell architecture probably plays an important role in the expression of the activity of the enzyme.…”