Streptozotocin Diabetes CORRELATION WITH EXTENT OF DEPRESSION OF PANCREATIC ISLET NICOTINAMIDE ADENINE DINUCLEOTIDE

Abstract

A B S T R A C T The diabetogenic activity of streptozotocin has been correlated with a reduction in pyridine nucleotide synthesis in the mouse pancreatic islet. To determine the specificity of this reduction for diabetogenicity, a comparative study of streptozotocin, its cytotoxic moiety, 1-methyl-1-nitrosourea, and alloxan was performed. Streptozotocin administered intraperitoneally (i.p.) producd a dose-related reduction in islet NAD which was proportional to the degree of diabetogenicity. A diabetogenic dose, 200 mg/kg, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.224 F'mol/ml and reduced the mean islet NAD from a control of 0.78 to 0.15 pmol. At borderline, 150 mg/kg, and nondiabetogenic, 100 mg/kg, doses, plasma concentrations reached 0.161 and 0.136 pmol/ml, and NAD was 0.36 and 0.86 pmol/islet, respectively. 1-Methyl-1-nitrosourea, 100 mg/kg, attained a maximum N-nitroso intact 1-methyl-1-nitrosourea concentration of 0.162 /mol/ ml and reduced the mean NAD to 0.58 pmol/islet, and was nondiabetogenic; 200 mg/kg attained a peak plasma concentration of 0.344 /mol/ml and depressed NAD to 0.38 pmol/islet, and was inconsistently diabetogenic. Islet NAD of 0.4 pmol/islet or greater is required for integrity of the beta cell. A diabetogenic dose of alloxan, 500 mg/kg, did not depress NAD, 0.85 pmol/islet, therefore confirming that its mechanism of diabetogenicity differs from that of streptozotocin.In vivo uptake of [methyl-"4C]streptozotocin by islets was 3.8 times that of [methyl-14C]-1-methyl-1-nitrosourea, whereas uptake by the exocrine pancreas favored 1-methyl-1-nitrosourea over streptozotocin 2.4:1. The decreased islet uptake of 1-methyl-1-nitrosourea correlates with the 3.5 times increased molar dosage required to produce islet NAD depression comparable to that of 3treptozotocin, 150 mg/kg. These studies indicate that

Evaluation of antidiabetic activity of fruit of Coriandrum sativum. Linn methanolic extract in Streptozocin induced diabetic wistar Albino rats

“…The action of STZ on mitochondria generates SOD anions, which leads to diabetic mellitus complications. [19][20][21] Glibenclamide, being as an Sulfonylurea derivative is often used as a standard antidiabetic drug in STZ-induced diabetes to compare the efficacy of a variety of antihyperglycemic drug compounds. Glibenclamide has been involved in stimulating insulin secretion from pancreatic β-cells principally by inhibiting ATP sensitive K + ATP channels in the plasma membrane.…”

Effects of streptozotocin in vitro on proinsulin biosynthesis, insulin release and ATP content of isolated rat islets of Langerhans

“…In agreement with this observation is the report by Dulin et al [19] who showed that in vivo 2-deoxyglucose, but not glucose, glucosamine or mannoheptulose protected against the diabetogenic action of streptozotocin. Yet Anderson et al [25] have demonstrated that the glucose carrier of methyl-14C-streptozotocin facilitates the uptake of its cytotoxic group, 1-methyl-l-nitrosourea, into islets. These authors have also shown that a dose of streptozotocin, which was diabetogenic when administered intra-peritoneally, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.22 mM and thus a concentration in the range of those used in vitro in the present studies.…”

“…Certainly, the administration of nicotinamide, a precursor of NAD in many tissues, protects against the diabetogenic effects of subsequently administered streptozotocin [17][18][19][20][21][22][23][24][25]. This protection may, however, unmask a long term oncogenic effect of the drug [26,27].Studies of the effects of streptozotocin on islets of Langerhans have shown a correlation between the extent of B-cell destruction and the decrease in islet NAD [25]; decreased oxidation of glucose by islets isolated after in vivo administration of a diabetogenic dose of streptozotocin [28]; and a dose-related inhibition of glucose-induced insulin secretion during two hours of incubation, when the drug was added in vitro to isolated islets [29]. The purpose of the present study was that of investigating the effects of streptozotocin on proinsulin synthesis, while simultaneously measuring its effects upon insulin release.…”

“…Certainly, the administration of nicotinamide, a precursor of NAD in many tissues, protects against the diabetogenic effects of subsequently administered streptozotocin [17][18][19][20][21][22][23][24][25]. This protection may, however, unmask a long term oncogenic effect of the drug [26,27].…”

Hypoglycemic and anti-diabetic activity of ethanolic extract of Catharanthus pusillus (murray) g.don

“…Non insulin dependent diabetes mellitus, type 2 (NIDDM) can be manifested by chronic hyperglycemia due to defects in insulin secretion, insulin action and or both [16] . It is common disorder among the Indian population.…”