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Hyperglycemia increases vascular adrenomedullin expression
M Hayashi1, T Shimosawa, T Fujita
1School of Medicine, University of Tokyo, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo, 112-8688, Japan. HAYASIMI-DIS@h.u-tokyo.ac.jp
Abstract:
We have reported that plasma adrenomedullin (AM) in hyperglycemic patients was significantly increased compared with normal volunteers. In this report we examined the effects of hyperglycemia on AM expression in the vasculature, the main site of AM production. AM mRNA level in the aorta was higher in the diabetic rats than in the control rats. AM mRNA level and protein kinase C (PKC) activity in cultured vascular smooth muscle cells (VSMC) increased as the glucose concentration in the medium changed from 100mg/dl to 450mg/dl. PKC inhibitors blocked this increase of AM mRNA. Similar osmotic change with mannitol had no effect on AM expression. We conclude that (1) hyperglycemia increases vascular AM expression through PKC-dependent pathway, and (2) the elevated plasma AM in hyperglycemic patients originates from the glucose induced vascular AM expression. We propose the possible role of AM in the pathogenesis of diabetic vascular complications.
Insights
Hyperglycemia elevates vascular adrenomedullin (AM) expression via a protein kinase C (PKC)-dependent pathway. This glucose-induced vascular AM contributes to increased plasma AM levels in hyperglycemic patients.
Area of Science:
- Endocrinology
- Vascular Biology
- Metabolic Syndrome
Background:
- Plasma adrenomedullin (AM) is elevated in hyperglycemic patients.
- The vasculature is a primary site for AM production.
- Understanding hyperglycemia's impact on vascular AM is crucial for diabetic complications.
Purpose of the Study:
- To investigate the effect of hyperglycemia on AM expression in the vasculature.
- To elucidate the signaling pathway involved in glucose-induced AM production.
- To determine if vascular AM contributes to elevated plasma AM levels.
Main Methods:
- Compared AM mRNA levels in aortas of diabetic and control rats.
- Cultured vascular smooth muscle cells (VSMC) exposed to varying glucose concentrations.
- Assessed protein kinase C (PKC) activity in VSMC.
- Utilized PKC inhibitors to block AM mRNA increase.
Main Results:
- Diabetic rats exhibited higher aortic AM mRNA levels than controls.
- High glucose concentrations (450 mg/dl) increased AM mRNA and PKC activity in VSMC.
- PKC inhibition prevented the glucose-induced rise in AM mRNA.
- Mannitol, an osmotic control, did not affect AM expression.
Conclusions:
- Hyperglycemia stimulates vascular AM expression through a PKC-dependent pathway.
- Elevated plasma AM in hyperglycemia likely originates from increased vascular AM production.
- Vascular AM may play a role in the pathogenesis of diabetic vascular complications.