Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects

Michael Koffler, Philip Raskin, Debra Womble, J. Harold Helderman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 ± 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 ± 4 at time 0 to 2 ± 2% sp Cr release (P < 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence. This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself.

Original languageEnglish (US)
Pages (from-to)364-370
Number of pages7
JournalDiabetes
Volume40
Issue number3
StatePublished - Mar 1991

Fingerprint

Insulin Receptor
Lymphocytes
Insulin
Isoantigens
Hyperinsulinism
Immunologic Cytotoxicity
Cell Membrane
T-Lymphocytes
Complement Receptors
Glucose Clamp Technique
Healthy Volunteers
Ligands
Membranes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects. / Koffler, Michael; Raskin, Philip; Womble, Debra; Helderman, J. Harold.

In: Diabetes, Vol. 40, No. 3, 03.1991, p. 364-370.

Research output: Contribution to journalArticle

Koffler, Michael ; Raskin, Philip ; Womble, Debra ; Helderman, J. Harold. / Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects. In: Diabetes. 1991 ; Vol. 40, No. 3. pp. 364-370.
@article{33eaae582866451181b60e38576e6fe9,
title = "Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects",
abstract = "Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25{\%} of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 ± 9{\%} of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 ± 4 at time 0 to 2 ± 2{\%} sp Cr release (P < 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence. This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself.",
author = "Michael Koffler and Philip Raskin and Debra Womble and Helderman, {J. Harold}",
year = "1991",
month = "3",
language = "English (US)",
volume = "40",
pages = "364--370",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects

AU - Koffler, Michael

AU - Raskin, Philip

AU - Womble, Debra

AU - Helderman, J. Harold

PY - 1991/3

Y1 - 1991/3

N2 - Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 ± 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 ± 4 at time 0 to 2 ± 2% sp Cr release (P < 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence. This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself.

AB - Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 ± 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 ± 4 at time 0 to 2 ± 2% sp Cr release (P < 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence. This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself.

UR - http://www.scopus.com/inward/record.url?scp=0025959694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025959694&partnerID=8YFLogxK

M3 - Article

VL - 40

SP - 364

EP - 370

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -