The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels

Moshe Phillip, Yael Segeve, Amnon Zung, Avinoam A. Kowarski, Haim Werner, Charles T. Roberts, Derek LeRoith, John Ladas, Susan E. Mulroney

Research output: Contribution to journalArticle

Abstract

Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/ml vs 30±5 (1-6 h); 23±10 (9-15 h); and 13±3 ng/ml (24-30 h post-STZ);P<0.05 for all STZ groups vs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control saline vs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.

Original languageEnglish (US)
Pages (from-to)689-693
Number of pages5
JournalEndocrine
Volume3
Issue number9
DOIs
StatePublished - Sep 1995
Externally publishedYes

Fingerprint

Streptozocin
Insulin-Like Growth Factor I
Kidney
Control Groups
Injections
Diabetes Complications
Area Under Curve
Sprague Dawley Rats
Neck
Catheters

Keywords

  • diabetes
  • growth hormone
  • IGF-I
  • kidney
  • rat

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Phillip, M., Segeve, Y., Zung, A., Kowarski, A. A., Werner, H., Roberts, C. T., ... Mulroney, S. E. (1995). The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels. Endocrine, 3(9), 689-693. https://doi.org/10.1007/BF02746346

The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels. / Phillip, Moshe; Segeve, Yael; Zung, Amnon; Kowarski, Avinoam A.; Werner, Haim; Roberts, Charles T.; LeRoith, Derek; Ladas, John; Mulroney, Susan E.

In: Endocrine, Vol. 3, No. 9, 09.1995, p. 689-693.

Research output: Contribution to journalArticle

Phillip, M, Segeve, Y, Zung, A, Kowarski, AA, Werner, H, Roberts, CT, LeRoith, D, Ladas, J & Mulroney, SE 1995, 'The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels', Endocrine, vol. 3, no. 9, pp. 689-693. https://doi.org/10.1007/BF02746346
Phillip, Moshe ; Segeve, Yael ; Zung, Amnon ; Kowarski, Avinoam A. ; Werner, Haim ; Roberts, Charles T. ; LeRoith, Derek ; Ladas, John ; Mulroney, Susan E. / The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels. In: Endocrine. 1995 ; Vol. 3, No. 9. pp. 689-693.
@article{6d8496c2494d4a55acc237074a503478,
title = "The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels",
abstract = "Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/ml vs 30±5 (1-6 h); 23±10 (9-15 h); and 13±3 ng/ml (24-30 h post-STZ);P<0.05 for all STZ groups vs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63{\%} of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control saline vs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.",
keywords = "diabetes, growth hormone, IGF-I, kidney, rat",
author = "Moshe Phillip and Yael Segeve and Amnon Zung and Kowarski, {Avinoam A.} and Haim Werner and Roberts, {Charles T.} and Derek LeRoith and John Ladas and Mulroney, {Susan E.}",
year = "1995",
month = "9",
doi = "10.1007/BF02746346",
language = "English (US)",
volume = "3",
pages = "689--693",
journal = "Endocrine",
issn = "1355-008X",
publisher = "Humana Press",
number = "9",

}

TY - JOUR

T1 - The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels

AU - Phillip, Moshe

AU - Segeve, Yael

AU - Zung, Amnon

AU - Kowarski, Avinoam A.

AU - Werner, Haim

AU - Roberts, Charles T.

AU - LeRoith, Derek

AU - Ladas, John

AU - Mulroney, Susan E.

PY - 1995/9

Y1 - 1995/9

N2 - Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/ml vs 30±5 (1-6 h); 23±10 (9-15 h); and 13±3 ng/ml (24-30 h post-STZ);P<0.05 for all STZ groups vs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control saline vs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.

AB - Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/ml vs 30±5 (1-6 h); 23±10 (9-15 h); and 13±3 ng/ml (24-30 h post-STZ);P<0.05 for all STZ groups vs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control saline vs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.

KW - diabetes

KW - growth hormone

KW - IGF-I

KW - kidney

KW - rat

UR - http://www.scopus.com/inward/record.url?scp=0029089236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029089236&partnerID=8YFLogxK

U2 - 10.1007/BF02746346

DO - 10.1007/BF02746346

M3 - Article

C2 - 21153228

AN - SCOPUS:0029089236

VL - 3

SP - 689

EP - 693

JO - Endocrine

JF - Endocrine

SN - 1355-008X

IS - 9

ER -