Abnormal Insulin Secretion in a Streptozocin Model of Diabetes: Effects of Insulin Treatment

We have proposed that chronic hyperglycemia causes the abnormal glucose influence on arginine-stimulated insulin secretion in the neonatal streptozocin (STZ) rat model of NIDDM and therefore studied the effect of 24h of mild insulin-induced hypoglycemia on this defect. Ultralente insulin, 20 U/kg, was given at 9 a.m. and 10 U/kg at 5 p.m., and insulin and glucagon secretion were then studied the next morning using the in vitro isolated, perfused pancreas. The fed plasma glucose concentrations decreased in the STZ rats from 191 ± 13 to 101 ± 9 mg/dl and from 133 ± 4 to 99 ± 8 mg/dl in the controls. As expected, 10 mM arginine caused a trivial insulin response at 2.8 mM glucose in the treated and untreated control groups compared with the marked one at 16.7 mM. The response to arginine at 2.8 mM glucose in the untreated STZ rats, however, was strikingly elevated (7.65 ± 2.29 versus 0.41 ± 0.16 ng/ml in the untreated controls) and it was not potentiated by the high glucose background, but the result at 2.8 mM glucose in the treated STZ rats was similar to that of the treated controls (0.46 ± 0.12 versus 0.16 ± 0.03 ng/ml). A returh of glucose influence on IBMX-stimulated insulin secretion was also noted. Glucose-induced insulin release, however, was not restored in the treated STZ rats, but it was markedly suppressed in the controls by the insulin treatment. Glucose influence on the glucagon response to arginine was maintained in the STZ model even though the glucagon release to a lowered glucose concentration was lost. These data suggest that chronic hyperglycemia causes the abnormal glucose influence on argininestimulated insulin release in the STZ model of diabetes.

[1]  J. Leahy,et al.  Abnormal Glucose Regulation of Insulin Secretion in Models of Reduced B-Cell Mass , 1984, Diabetes.

[2]  W. J. Andrews,et al.  Insulin Therapy in Obese, Non-insulin-dependent Diabetes Induces Improvements in Insulin Action and Secretion that Are Maintained for Two Weeks After Insulin Withdrawal , 1984, Diabetes.

[3]  S. Bonner-Weir,et al.  Abnormal Islet and Adipocyte Function in Young B-cell-deficient Rats with Near-Normoglycemia , 1984, Diabetes.

[4]  B. Portha,et al.  Glucose Insensitivity and Amino-acid Hypersensitivity of Insulin Release in Rats with Non-insulin-dependent Diabetes: A Study with the Perfused Pancreas , 1983, Diabetes.

[5]  J. Palmer,et al.  Glucose Modulation of Insulin and Glucagon Secretion in Nondiabetic and Diabetic Man , 1982, Diabetes.

[6]  J. P. Moulin,et al.  The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia. , 1982, Metabolism: clinical and experimental.

[7]  S. Aronoff,et al.  Improvement of insulin secretion but not insulin resistance after short term control of plasma glucose in obese type II diabetics. , 1982, The Journal of clinical endocrinology and metabolism.

[8]  S. Bonner-Weir,et al.  Islet Secretion in a New Experimental Model for Non-insulin-dependent Diabetes , 1981, Diabetes.

[9]  S. Bonner-Weir,et al.  Responses of Neonatal Rat Islets to Streptozotocin: Limited B-Cell Regeneration and Hyperglycemia , 1981, Diabetes.

[10]  E. Cerasi,et al.  Glucose memory of pancreatic B and A2 cells: evidence for common time-dependent actions of glucose on insulin and glucagon secretion in the perfused rat pancreas. , 1979, The Journal of clinical investigation.

[11]  J. Halter,et al.  Potentiation of insulin secretory responses by plasma glucose levels in man: evidence that hyperglycemia in diabetes compensates for imparied glucose potentiation. , 1979, The Journal of clinical endocrinology and metabolism.

[12]  G. Grodsky,et al.  Effect of continuous insulin infusion with an implantable seven-day minipump in the diabetic Chinese hamster. , 1979, Endocrinology.

[13]  D. Elahi,et al.  Pancreatic α- and β-cell responses to GIP infusion in normal man , 1979 .

[14]  V. Go,et al.  Direct effect of insulin on secretion of insulin, glucagon, gastric inhibitory polypeptide, and gastrin during maintenance of normoglycemia. , 1978, The Journal of clinical endocrinology and metabolism.

[15]  E. Cerasi,et al.  Quantitative Determination of the Interaction Between Epinephrine and Various Insulin Releasers in Man , 1978, Diabetes.

[16]  R. Holman,et al.  Beta-cell function improved by supplementing basal insulin secretion in mild diabetes. , 1976, British medical journal.

[17]  E. Cerasi.  Potentiation of insulin release by glucose in man. II. Role of the insulin response, and enhancement of stimuli other than glucose. , 1975, Acta endocrinologica.

[18]  G. Grodsky,et al.  Characterization of the effects of arginine and glucose on glucagon and insulin release from the perfused rat pancreas. , 1974, The Journal of clinical investigation.

[19]  F. Matschinsky,et al.  Glucose modulation of amino acid-induced glucagon and insulin release in the isolated perfused rat pancreas. , 1974, The Journal of clinical investigation.

[20]  M. Williams,et al.  A simple and inexpensive membrane "lung" for small organ perfusion. , 1974, Journal of lipid research.

[21]  S. D. Knowlton,et al.  Glucagon Secretion from the Perfused Rat Pancreas , 1974 .

[22]  R. Turner,et al.  A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. , 1972, Acta endocrinologica.

[23]  G. Grodsky,et al.  Relationships between arginine and glucose in the induction of insulin secretion from the isolated, perfused rat pancreas. , 1972, Endocrinology.