GLUCONEOGENESIS AND CELLULAR INJURY. A FURTHER INQUIRY INTO THE MECHANISM INVOLVED IN DIABETES ENHANCED BY INFLAMMATION

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Abstract
An acute inflammation in a depancreatized dog is accompanied by a marked degree of local gluconeogenesis. The surplus glucose formed in the inflamed area from products of local protein breakdown diffuses into the circulation, enhancing thus the existing state of hypcrglycemia. The conc. of exudate sugar is at a consistently higher level than the blood sugar from the very beginning of the inflammatory reaction. When the inflammation has progressed for 1 day, the conc. of blood sugar tends to approach that of the exudate sugar. The establishment of a conc. gradient between the level of exudate and blood sugar strongly supports the view of a gluconeogenetic process at the site of inflammation. A similar gradient, though not as marked, exists between the urea conc. of exudate and that of blood. The difference in the magnitude of the glucose and urea conc. gradient seems to be primarily referable to the respective diffusion coefficient of these 2 substances. The extent of proteolysis in the exudate of a diabetic dog is definitely more marked than in that of a nondiabetic animal. These facts add further support to previous observations that gluconeogenesis in the inflamed area of a diabetic animal is associated with enhanced local protein catabolism. The process of local glucose formation is not primarily referable to the presence of leukocytes but rather to cells in general injured at the site of inflammation. In a non-diabetic animal the conc. of sugar in exudate is at first higher than that in blood. This effect, however, is transient. This, in turn, is contrary to the findings in diabetic dogs. After the inflammation has progressed from several hrs. to about a day, the sugar level in exudate of non-diabetic dogs drops to a level usually below that of the blood sugar. This lowering in exudate sugar conc. is referable to an increase in the local glycolytic reaction which thus overshadows the initial effect of glucose formation at the site of an acute inflammation. If, at the beginning of inflammation in a non-diabetic animal, the degree of local gluconeogenesis is marked, the effect may be reflected in the circulation inducing thus a transient hyperglycemia. The available evidence suggests that the temporary elevation in exudate sugar in the inflamed area of a non-diabetic animal is primarily referable to local gluconeogenesis. The difference in reaction from that in diabetic dogs is quantitative in nature. In the latter local gluconeogenesis is sustained and exaggerated. The effect of abundant glucose production in depancreatized animals cannot be readily obliterated by the slightly elevated local glycolysis. The consequence is constant gluconeogenesis; the glucose in turn diffuses into the circulating blood, thus enhancing the diabetic condition. In brief, injured cells, as manifested by inflammation in both diabetic and non-diabetic animals, are characterized by an increase in their protein catabolic processes and by potentially becoming foci of gluconeogenesis.

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