The additive effects of glucose and insulin on the proliferation of infragenicular vascular smooth muscle cells

Avena, Ricardo; Mitchell, Marc; Neville, Richard F.; Sidawy, Anton N.

doi:10.1016/s0741-5214(98)70029-1

Cited by 35 publications

(26 citation statements)

References 19 publications

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“…Our observations are consistent with an earlier study reporting that PDGF-induced VSMC proliferation was similar under low and elevated glucose conditions (39). It is unlikely that the passage number of cells used in our study (P3-P5) could explain either discrepant or comparable results discussed here, since those studies typically used P2-P5 cells (2,11,49). One study did, however, report using cells of higher passage (P6 -P10) (6).…”

Section: Discussionsupporting

confidence: 91%

“…However, in response to insulin plus PDGF, there was no difference in proliferation between the two SV-SMC populations. Earlier investigations using human and primate SMC of both nondiabetic (31,38) and diabetic (2,46) origin demonstrated that insulin promoted cell proliferation. Although each of these studies provided evidence that insulin is a potent mitogen for VSMC, ours is the first to directly investigate the effects of insulin on SV-SMC from nondiabetic and diabetic patients in a side-by-side manner.…”

Section: Discussionmentioning

confidence: 99%

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Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Madi

Riches

Warburton

et al. 2009

American Journal of Physiology-Cell Physiology

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Madi HA, Riches K, Warburton P, O'Regan DJ, Turner NA, Porter KE. Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients. Am J Physiol Cell Physiol 297: C1307-C1317, 2009. First published September 9, 2009 doi:10.1152/ajpcell.00608.2008.-Individuals with Type 2 diabetes mellitus (T2DM) are at increased risk of saphenous vein (SV) graft stenosis following coronary artery bypass. Graft stenosis is caused by intimal hyperplasia, a pathology characterized by smooth muscle cell (SMC) proliferation and migration. We hypothesized that SV-SMC from T2DM patients were intrinsically more proliferative and migratory than those from nondiabetic individuals. SV-SMC were cultured from nondiabetic and T2DM patients. Cell morphology (light microscopy, immunocytochemistry), S100A4 expression (real-time RT-PCR, immunoblotting), proliferation (cell counting), migration (Boyden chamber assay), and cell signaling (immunoblotting with phosphorylation state-specific antibodies) were studied. SV-SMC from T2DM patients were morphologically distinct from nondiabetic patients and exhibited a predominantly rhomboid phenotype, accompanied by disrupted F-actin cytoskeleton, disorganized ␣-smooth muscle actin network, and increased focal adhesion formation. However, no differences were observed in expression of the calcium-binding protein S100A4, a marker of rhomboid SMC phenotype, between the two cell populations. T2DM cells were less proliferative in response to fetal calf serum than nondiabetic cells, but both populations had similar proliferative responses to insulin plus PDGF. Under high glucose concentration conditions in the presence of insulin, migration of diabetic SV-SMC was greater than nondiabetic cells. Glucose concentration did not affect SV-SMC proliferation. No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3␤) were apparent between the two populations. In conclusion, SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a rhomboid phenotype and are more migratory, but less proliferative, in response to serum. diabetes mellitus; vein graft stenosis; metabolic memory DIABETES MELLITUS IS A SERIOUS and escalating health problem worldwide (3) that currently affects more than 2

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Madi

Riches

Warburton

et al. 2009

American Journal of Physiology-Cell Physiology

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“…Insulin is a powerful vasodilator, 19,20 and the insulin-resistant state that commonly accompanies obesity 21 impairs the vasodilatory effect of insulin, linking the insulin resistant state and obesity with vascular endothelial dysfunction. 22 The higher levels of circulating insulin in the insulin resistant state may also be associated with vascular effects, such as proliferation of smooth muscle cells 23 and increases in collagen production. 24 High levels of glucose, as found in the insulin resistant state, have been shown to stimulate collagen synthesis and cross-linking between protein fibers.…”

Section: Discussionmentioning

confidence: 99%

Weight Change Is Associated With Change in Arterial Stiffness Among Healthy Young Adults

et al. 2005

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Abstract-Risk factors for arterial stiffness progression have not been well characterized. We examined the relationship between arterial stiffness progression and body weight and weight gain in a group of healthy young adults. Aortic pulse-wave velocity was assessed at 2 time points approximately 2 years apart in 152 white and black adults aged 20 to 40 years, and was standardized by the time between visits to obtain annualized pulse-wave velocity changes. Blacks had 15.5 cm/s per year larger annual pulse-wave velocity increases compared with whites (Pϭ0.02), even after multivariable adjustment for weight and blood pressure changes. Larger annual pulse-wave velocity increases were also associated with larger baseline body weight (Pϭ0.02), waist girth (Pϭ0.003), and body mass index (PϽ0.001), and greater annual weight gain (Pϭ0.02), after adjustment for baseline pulse-wave velocity. After multivariable adjustment that included blood pressure changes, larger baseline waist girth (Pϭ0.009), baseline body mass index (Pϭ0.001), body mass index increase (Pϭ0.037), and weight gain (Pϭ0.017) remained significantly associated with larger annual pulse-wave velocity progression. Weight change showed a direct relationship with pulse-wave velocity change; mean annual pulse-wave velocity changes were Ϫ29.9 cm/s per year (regression) for those with Ն4.5 kg annual weight loss and 18.2 cm/s per year (progression) for those with Ն4.5 kg annual weight gain. These data show strong associations between weight gain and arterial stiffness progression, as well as between weight loss and arterial stiffness regression. These data greatly underscore the vascular benefit of weight loss. Successful weight loss programs in young adults, particularly blacks, are needed.

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“…Proatherogenic effects of insulin include stimulation of proliferation of vascular smooth muscle cells, as well as production of plasminogen activator inhibitor 1 by these cells (29,30). In contrast, insulin may protect against atherosclerosis by antagonizing inflammatory transcription factors, inhibiting adhesion molecule expression, and promoting nitric oxide production in endothelial cells (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

et al. 2005

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The rising prevalence of the insulin resistance syndrome in our society necessitates a better understanding of the genetic determinants of all aspects of insulin action and metabolism. We evaluated the heritability of insulin sensitivity and the metabolic clearance rate of insulin (MCRI) as quantified by the euglycemic-hyperinsulinemic clamp in 403 Mexican Americans. We tested the candidate gene AMP deaminase 1 (AMPD1) for association with insulin-related traits because it codes for an enzyme that has the potential to influence multiple aspects of insulin pharmacodynamics. By converting AMP to inosine monophosphate, AMPD1 plays a major role in regulating cellular AMP levels; AMP activates AMP kinase, an enzyme that modulates cellular energy and insulin action. We determined that nine AMPD1 single nucleotide polymorphisms (SNPs) defined two haplotype blocks. Insulin clearance was found to have a higher heritability (h 2 ‫؍‬ 0.58) than fasting insulin (h 2 ‫؍‬ 0.38) or insulin sensitivity (h 2 ‫؍‬ 0.44). The MCRI was associated with AMPD1 SNPs and haplotypes. Insulin clearance is a highly heritable trait, and specific haplotypes within the AMPD1 gene, which encodes a skeletal muscle؊specific protein, are associated with variation in insulin clearance. We postulated that the processes of insulin action and insulin clearance in skeletal muscle are highly regulated and that AMPD1 function may play an important role in these phenomena. Diabetes 54: 1222-1227, 2005 T he insulin resistance syndrome (also called the metabolic syndrome) is a clustering of factors associated with an increased risk of coronary artery disease (1). In the U.S., Ͼ20% of adults are affected by it (2). Mexican Americans have a high prevalence of hyperinsulinemia and insulin resistance as well as the highest age-specific prevalence of the insulin resistance syndrome (2-4). Thus, by studying a large familybased sample of Mexican-American subjects, we sought to elucidate the genetic determinants of insulin metabolism and action.In pursuit of this goal, we evaluated insulin phenotypes using the euglycemic-hyperinsulinemic clamp study. Assessment of the glucose infusion rate (M) during the euglycemic-hyperinsulinemic clamp is regarded as the most direct physiological measurement of insulin sensitivity (5,6). The clamp also allows calculation of the metabolic clearance rate of insulin (MCRI). In this family-based study, we assessed the variation of these traits within families and observed for the first time a high heritability for MCRI. To begin to identify specific genes that mediate heritability of insulin-related phenotypes, we selected a candidate gene, AMP deaminase 1 (AMPD1), which has been shown to influence skeletal muscle adenine nucleotide levels (7) and which in turn could have effects on other enzymes, such as AMP-activated protein kinase (AMPK), that are known to influence insulin action (8). We show herein that polymorphisms in AMPD1 are associated with variation in the MCRI. RESEARCH DESIGN AND METHODSThe University of California at Lo...

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The additive effects of glucose and insulin on the proliferation of infragenicular vascular smooth muscle cells

Abstract: Both insulin and glucose stimulate the growth of diabetic infragenicular VSMCs. The mitogenic effects of insulin and glucose are additive and may contribute to the development of atherosclerosis in patients with DM.

Cited by 35 publications

References 19 publications

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Weight Change Is Associated With Change in Arterial Stiffness Among Healthy Young Adults

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

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