Enhancement of Glucose-Stimulated Insulin Secretion From Isolated Rat Pancreatic Islets by Human Insulin Antibodies

Hahn, Hans-Jürgen; Menzel, R; Gottschling, Hubert; Jahr, D

doi:10.1530/acta.0.0830123

Cited by 13 publications

(5 citation statements)

References 10 publications

(13 reference statements)

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“…They observed pancreatic P-cell hyperplasia in a patient with recurrent hypoglycemia and insulin-binding antibodies; another patient showed markedly elevated plasma insulin and C-peptide levels during oral glucose tolerance testing, which were similar in our patient (7). In addition, human sera containing insulin antibodies have been reported to enhance glucose-stimulated insulin secretion from isolated rat pancreatic islets (28). Therefore, it is conceivable that the inappropriate suppression of endogenous insulin secretion during hypoglycemia in S.M.…”

Section: Fig 3 Sm's Serum Preadsorbed With In* Creasing Concentrasupporting

confidence: 82%

Spontaneous Hypoglycemia Associated With Autoimmunity Specific to Human Insulin

et al. 1987

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A 55-yr-old woman with a history of Graves' disease experienced attacks of postprandial hypoglycemia for 6 yr. An insulinoma could not be confirmed by repeated fasting tests and by surgical pancreas revision. Extracted pancreatic insulin was chemically normal. Fasting plasma total insulin (1.22 nM = 183 microU/ml) and proinsulin (0.48 nM) were elevated and greatly increased after oral glucose. Glucose-clamp studies revealed delayed insulin clearance. Plasma free-insulin levels were normal. Insulin-binding antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay with human insulin as ligand but not with pork or beef insulins. Analysis with a modified ELISA suggested a monotypic and monoclonal human insulin autoantibody, which showed a restriction to the lambda-light chain. T-lymphocytes (predominantly helper) demonstrated increased responsiveness to beef, pork, and human insulins by proliferation assay. A T-lymphocyte line showed exclusively human insulin specificity. All this indicated cellular and humoral anti-human insulin autoimmunities. Clinically, the cause of hypoglycemia associated with elevated total insulin and proinsulin was misdiagnosed as atypical insulinoma. The study of total and free plasma insulin levels and sensitive antibody assays specific to human insulin were necessary to correctly diagnose autoimmune hypoglycemia.

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Section: Fig 3 Sm's Serum Preadsorbed With In* Creasing Concentrasupporting

confidence: 82%

Spontaneous Hypoglycemia Associated With Autoimmunity Specific to Human Insulin

et al. 1987

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“…In addition, factors such as insulin resistance and secretion of contrainsulin hormones may also determine whether or not hypoglycemia will occur at a particular time. Furthermore, an enhanced output of insulin in the presence of insulin antibodies has been documented in vitro with isolated rat islet tissue (37). This circumstance may contribute to the hypoglycemic syndrome, although clearly the secreted insulin would be bound by antibodies, and dissociation would still be required for its hypoglycemic action.…”

Section: Discussionmentioning

confidence: 97%

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Goldman¹,

Baldwin²,

Rubenstein³

et al. 1979

J. Clin. Invest.

137

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A B S T R A C T Five patients with fasting and(or) postprandial hypoglycemia were found to have insulin antibodies in the absence of previously documented immunization. Studies on the equilibrium-binding of insulin to the autoantibodies revealed two classes of binding sites with association constants and binding capacities analogous to those of insulin antibodies from insulin-treated diabetic patients. Similarly, no consistent differences in these parameters were found in both groups of patients with insulins ofbovine, porcine, and human origin. Proinsulin (C-segment directed) antibodies capable ofbinding bovine or porcine proinsulin were present in 10 of 10 and 9 of 10 insulin-treated diabetics serving as controls, respectively, and, when present, provide incontrovertible evidence of exogenous insulin administration. No such antibodies could be detected in the hypoglycemic patients with autoimmune insulin antibodies.The kinetics of dissociation of the insulin-antibody complexes were consistent with the existence of two classes of antibody sites. The corresponding dissociation rate constants were large enough to predict that significant amounts of free hormone may be generated by this mechanism and provide a plausible pathogenesis for the hypoglycemia in these patients.

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“…Insulin release appears to reach a near maximum at a glucose level of 300-400 mg/dl in the perfused rat pancreas (31) and in isolated rat islets (32,33). In addition, the glucose level at half-maximal insulin output in rat islets, 160-180 mg/dl (33), is similar to the PG50 for normal humans in the present study, which is 197±20 mg/dl.…”

Section: Discussionmentioning

confidence: 99%

Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.

Ward¹,

Bolgiano²,

McKnight³

et al. 1984

J. Clin. Invest.

478

371

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Abstract. In order to assess whether patients with noninsulin-dependent diabetes mellitus (NIDDM) possess normal insulin secretory capacity, maximal B cell responsiveness to the potentiating effects of glucose was estimated in eight untreated patients with NIDDM and in eight nondiabetic controls. The acute insulin response to 5 g intravenous arginine was measured at five matched plasma glucose levels that ranged from 100-615 mg/dl. The upper asymptote approached by acute insulin responses (AIRma.) and the plasma glucose concentration at half-maximal responsiveness (PG50) were estimated using nonlinear regression to fit a modification of the Michaelis-Menten equation. In addition, glucagon responses to arginine were measured at these same glucose levels to compare maximal A cell suppression by hyperglycemia in diabetics and controls.Insulin responses to arginine were lower in diabetics than in controls at all matched glucose levels (P < 0.001 at all levels). In addition, estimated AIRma. was much lower in diabetics than in controls (83±21 vs. 450±93 MU/ml, P < 0.01). In contrast, PG50 was similar in diabetics and controls (234±28 vs. 197±20 mg/dl, P equals NS) and insulin responses in both groups approached or attained maxima at a glucose level of -460 mg/dl. Acute glucagon responses to arginine in patients with NIDDM were significantly higher than responses in controls at all glucose levels. In addition, although glucagon responses in control subjects reached a minimum at a glucose level of -460 mg/dl, responses

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Enhancement of Glucose-Stimulated Insulin Secretion From Isolated Rat Pancreatic Islets by Human Insulin Antibodies

Cited by 13 publications

References 10 publications

Spontaneous Hypoglycemia Associated With Autoimmunity Specific to Human Insulin

Spontaneous Hypoglycemia Associated With Autoimmunity Specific to Human Insulin

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.

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