Memory IgM protects endogenous insulin from autoimmune destruction

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.

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IMMUNOLOGICAL REACTIVITY OF INSULIN IN HUMAN SERUM

Acta Endocrinologica ◽

10.1530/acta.0.0530673 ◽

1966 ◽

Vol 53 (4) ◽

pp. 673-680 ◽

Cited By ~ 5

Author(s):

Torsten Deckert ◽

Kai R. Jorgensen

Keyword(s):

Normal Subjects ◽

The Other ◽

Human Pancreas ◽

Porcine Pancreas ◽

Crystalline Insulin ◽

Endogenous Insulin ◽

Significant Difference ◽

Human Sera ◽

Normal Human ◽

The One

ABSTRACT The purpose of this study was to investigate whether a difference could be demonstrated between crystalline insulin extracted from normal human pancreas, and crystalline insulin extracted from bovine and porcine pancreas. Using Hales & Randle's (1963) immunoassay no immunological differences could be demonstrated between human and pig insulin. On the other hand, a significant difference was found, between pig and ox insulin. An attempt was also made to determine whether an immunological difference could be demonstrated between crystalline pig insulin and crystalline human insulin from non diabetic subjects on the one hand and endogenous, circulating insulin from normal subjects, obese subjects and diabetic subjects on the other. No such difference was found. From these experiments it is concluded that endogenous insulin in normal, obese and diabetic human sera is immunologically identical with human, crystalline insulin from non diabetic subjects and crystalline pig insulin.

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Impact of Endogenous Insulin Adjustment Methods on the Assessment of Insulin Pharmacokinetics and Pharmacodynamics

Diabetes ◽

10.2337/db18-1051-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1051-P

Author(s):

SANG M. CHUNG ◽

JUSTIN A. PENZENSTADLER ◽

MANOJ KHURANA ◽

CHANDRAHAS SAHAJWALLA

Keyword(s):

Pharmacokinetics And Pharmacodynamics ◽

Insulin Pharmacokinetics ◽

Endogenous Insulin

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Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses

Diabetes ◽

10.2337/diabetes.41.9.1141 ◽

1992 ◽

Vol 41 (9) ◽

pp. 1141-1150 ◽

Cited By ~ 20

Author(s):

Q. Z. Liu ◽

W. C. Knowler ◽

R. G. Nelson ◽

M. F. Saad ◽

M. A. Charles ◽

...

Keyword(s):

Insulin Treatment ◽

Insulin Concentration ◽

Pima Indians ◽

Cross Sectional ◽

Endogenous Insulin ◽

Ecg Abnormalities ◽

Prospective Analyses

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Autoimmune destruction of islets transplanted into RT6-depleted diabetes-resistant BB/Wor rats

Diabetes ◽

10.2337/diabetes.39.5.643 ◽

1990 ◽

Vol 39 (5) ◽

pp. 643-645 ◽

Cited By ~ 2

Author(s):

P. A. Gottlieb ◽

J. P. Berrios ◽

G. Mariani ◽

E. S. Handler ◽

D. Greiner ◽

...

Keyword(s):

Autoimmune Destruction

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Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r1035 ◽

1988 ◽

Vol 255 (6) ◽

pp. R1035-R1040

Author(s):

R. Hoo-Paris ◽

M. L. Jourdan ◽

L. C. Wang ◽

R. Rajotte

Keyword(s):

Insulin Secretion ◽

Plasma Glucose ◽

Low Temperatures ◽

Plasma Insulin ◽

Glucose Utilization ◽

Exogenous Insulin ◽

Metabolic Substrate ◽

Endogenous Insulin ◽

Dose Dependent Decrease ◽

Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

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Intraperitoneal insulin administration in pigs: effect on circulating insulin and glucose levels

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001929 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001929

Author(s):

Ilze Dirnena-Fusini ◽

Marte Kierulf Åm ◽

Anders Lyngvi Fougner ◽

Sven Magnus Carlsen ◽

Sverre Christian Christiansen

Keyword(s):

Systemic Circulation ◽

Subcutaneous Insulin ◽

Insulin Levels ◽

Glucose Levels ◽

Endogenous Insulin ◽

Blood Glucose Levels ◽

Intraperitoneal Insulin ◽

A Minor ◽

Design And Methods ◽

Mean Blood Glucose

IntroductionThe effect of intraperitoneal insulin infusion has limited evidence in the literature. Therefore, the aim of the study was to investigate the pharmacokinetics and pharmacodynamics of different intraperitoneal insulin boluses. There is a lack of studies comparing the insulin appearance in the systemic circulation after intraperitoneal compared with subcutaneous insulin delivery. Thus, we also aimed for a comparison with the subcutaneous route.Research design and methodsEight anesthetized, non-diabetic pigs were given three different intraperitoneal insulin boluses (2, 5 and 10 U). The order of boluses for the last six pigs was randomized. Endogenous insulin and glucagon release were suppressed by repeated somatostatin analog injections. The first pig was used to identify the infusion rate of glucose to maintain stable glucose values throughout the experiment. The estimated difference between insulin boluses was compared using two-way analysis of variance (GraphPad Prism V.8).In addition, a trial of three pigs which received subcutaneous insulin boluses was included for comparison with intraperitoneal insulin boluses.ResultsDecreased mean blood glucose levels were observed after 5 and 10 U intraperitoneal insulin boluses compared with the 2 U boluses. No changes in circulating insulin levels were observed after the 2 and 5 U intraperitoneal boluses, while increased circulating insulin levels were observed after the 10 U intraperitoneal boluses. Subcutaneously injected insulin resulted in higher values of circulating insulin compared with the corresponding intraperitoneal boluses.ConclusionsSmaller intraperitoneal boluses of insulin have an effect on circulating glucose levels without increasing insulin levels in the systemic circulation. By increasing the insulin bolus, a major increase in circulating insulin was observed, with a minor additive effect on circulating glucose levels. This is compatible with a close to 100% first-pass effect in the liver after smaller intraperitoneal boluses. Subcutaneous insulin boluses markedly increased circulating insulin levels.

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