Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes

C. B. Guzmán; M. Walsh; V. Reddy; V. Donthireddy; F. Mahmood; A. Bode; J. R. Turner; S. J. Jacober; J. R. Sowers

doi:10.1053/meta.2001.19521

Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes

C. B. Guzmán, M. Walsh, V. Reddy, V. Donthireddy, F. Mahmood, A. Bode, J. R. Turner, S. J. Jacober, J. R. Sowers

Research output: Contribution to journal › Article › peer-review

Abstract

Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 ± 3 fmol/mL in controls v 23.1 ± 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (βE₂) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.

Original language	English (US)
Pages (from-to)	151-156
Number of pages	6
Journal	Metabolism: clinical and experimental
Volume	50
Issue number	2
DOIs	https://doi.org/10.1053/meta.2001.19521
State	Published - 2001
Externally published	Yes

Bibliographical note

Funding Information:
From the Division of Endocrinology, Diabetes and Hypertension, State University of New York Health Science Center at Brooklyn, Brooklyn; Department of Veterans Affairs Medical Center at Brooklyn, Brooklyn, NY; Department of Exercise and Movement Science, University of Oregon, Eugene, OR; and Department of Pathology and Division of Endocrinology, Metabolism and Hypertension, Wayne State University, Detroit, MI. Submitted November 15, 1999; accepted July 17, 2000. Supported by National Institutes of Health Grant No. DK-02503 (J.R.T.). Address reprint requests to J.R. Sowers, MD, Professor of Medicine and Cell Biology, Director, Endocrinology, Diabetes and Hypertension, SUNY Health Science Center at Brooklyn, 450 Clarkson Ave, Box 1205, Brooklyn, NY 11203. Copyright © 2001 by W.B. Saunders Company 0026-0495/01/5002-0026$35.00/0 doi:10.1053/meta.2001.19521

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title = "Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes",

abstract = "Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 ± 3 fmol/mL in controls v 23.1 ± 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (βE2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.",

author = "Guzm{\'a}n, {C. B.} and M. Walsh and V. Reddy and V. Donthireddy and F. Mahmood and A. Bode and Turner, {J. R.} and Jacober, {S. J.} and Sowers, {J. R.}",

note = "Funding Information: From the Division of Endocrinology, Diabetes and Hypertension, State University of New York Health Science Center at Brooklyn, Brooklyn; Department of Veterans Affairs Medical Center at Brooklyn, Brooklyn, NY; Department of Exercise and Movement Science, University of Oregon, Eugene, OR; and Department of Pathology and Division of Endocrinology, Metabolism and Hypertension, Wayne State University, Detroit, MI. Submitted November 15, 1999; accepted July 17, 2000. Supported by National Institutes of Health Grant No. DK-02503 (J.R.T.). Address reprint requests to J.R. Sowers, MD, Professor of Medicine and Cell Biology, Director, Endocrinology, Diabetes and Hypertension, SUNY Health Science Center at Brooklyn, 450 Clarkson Ave, Box 1205, Brooklyn, NY 11203. Copyright {\textcopyright} 2001 by W.B. Saunders Company 0026-0495/01/5002-0026$35.00/0 doi:10.1053/meta.2001.19521",

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AU - Guzmán, C. B.

AU - Walsh, M.

AU - Reddy, V.

AU - Donthireddy, V.

AU - Mahmood, F.

AU - Bode, A.

AU - Turner, J. R.

AU - Jacober, S. J.

AU - Sowers, J. R.

N1 - Funding Information: From the Division of Endocrinology, Diabetes and Hypertension, State University of New York Health Science Center at Brooklyn, Brooklyn; Department of Veterans Affairs Medical Center at Brooklyn, Brooklyn, NY; Department of Exercise and Movement Science, University of Oregon, Eugene, OR; and Department of Pathology and Division of Endocrinology, Metabolism and Hypertension, Wayne State University, Detroit, MI. Submitted November 15, 1999; accepted July 17, 2000. Supported by National Institutes of Health Grant No. DK-02503 (J.R.T.). Address reprint requests to J.R. Sowers, MD, Professor of Medicine and Cell Biology, Director, Endocrinology, Diabetes and Hypertension, SUNY Health Science Center at Brooklyn, 450 Clarkson Ave, Box 1205, Brooklyn, NY 11203. Copyright © 2001 by W.B. Saunders Company 0026-0495/01/5002-0026$35.00/0 doi:10.1053/meta.2001.19521

PY - 2001

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N2 - Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 ± 3 fmol/mL in controls v 23.1 ± 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (βE2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.

AB - Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 ± 3 fmol/mL in controls v 23.1 ± 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (βE2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.

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Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes

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Bibliographical note

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