Abstract
To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 265 |
| Issue number | 3 28-3 |
| State | Published - 1993 |
| Externally published | Yes |
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Keywords
- dexamethasone
- expression
- messenger ribonucleic acid
- mifepristone
- obesity rat
- pancreas
- pancreatic perfusion
- RU- 486
- secretion
- ZDF/drt
- Zucker
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
Cite this
Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia. / Pieber, T. R.; Stein, Daniel T.; Ogawa, A.; Alam, T.; Ohneda, M.; McCorkle, K.; Chen, L.; McGarry, J. D.; Unger, R. H.
In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 265, No. 3 28-3, 1993.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia
AU - Pieber, T. R.
AU - Stein, Daniel T.
AU - Ogawa, A.
AU - Alam, T.
AU - Ohneda, M.
AU - McCorkle, K.
AU - Chen, L.
AU - McGarry, J. D.
AU - Unger, R. H.
PY - 1993
Y1 - 1993
N2 - To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.
AB - To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.
KW - dexamethasone
KW - expression
KW - messenger ribonucleic acid
KW - mifepristone
KW - obesity rat
KW - pancreas
KW - pancreatic perfusion
KW - RU- 486
KW - secretion
KW - ZDF/drt
KW - Zucker
UR - http://www.scopus.com/inward/record.url?scp=0027424705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027424705&partnerID=8YFLogxK
M3 - Article
C2 - 8105694
AN - SCOPUS:0027424705
VL - 265
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 3 28-3
ER -