Central Action of Insulin Regulates Pulsatile Luteinizing Hormone Secretion in the Diabetic Sheep Model
This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin. Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that is normally present in the CSF when LH secret...
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Published in | Biology of reproduction Vol. 62; no. 5; pp. 1256 - 1261 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Society for the Study of Reproduction
01.05.2000
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Subjects | |
Online Access | Get full text |
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Summary: | This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin.
Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that
is normally present in the CSF when LH secretion is maintained by peripheral insulin administration. In the first experiment,
we monitored cerebrospinal fluid (CSF) insulin concentrations every 3â5 h in four diabetic sheep given insulin by peripheral
injection (30 IU). The insulin concentration in the CSF was increased after insulin injection, and there was a positive relationship
between CSF and plasma concentrations of insulin ( r = 0.80, P < 0.01). In the second experiment, peripheral insulin administration was discontinued, and the sheep received either an intracerebroventricular
(i.c.v.) infusion of insulin (12 mU/day in 2.4 ml saline) or saline (2.4 ml/day) for 5 days (n = 6) in a crossover design.
The dose of insulin (i.c.v.) was calculated to approximate the increase in CSF insulin concentration found after peripheral
insulin treatment. To monitor LH secretory patterns, blood samples were collected by jugular venipuncture at 10-min intervals
for 4 h on the day before and 5 days after the start of i.c.v. insulin infusion. To monitor the increase in CSF insulin concentrations,
a single CSF sample was collected one and four days after the start of the central infusion. The i.c.v. insulin infusion increased
CSF insulin concentrations above those in saline-treated animals ( P < 0.05) and maintained them at or above the peak levels achieved after peripheral insulin treatment. Central insulin infusion
did not affect peripheral (plasma) insulin or glucose concentrations. LH pulse frequency in insulin-treated animals was greater
than that in saline-treated animals (3.5 ± 0.2 vs. 2.3 ± 0.3 pulses/4 h, P < 0.01), but it was less than that during peripheral insulin treatment (4.8 ± 0.2 pulses/4 h, P < 0.01). Our findings suggest that physiologic levels of central insulin supplementation are able to increase pulsatile LH
secretion in diabetic sheep with low peripheral insulin. These results are consistent with the notion that central insulin
plays a role in regulating pulsatile GnRH secretion. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-3363 1529-7268 |
DOI: | 10.1095/biolreprod62.5.1256 |