Insulin and glucose play a role in foam cell formation and function

Pavel N. Shashkin, Nitin Jain, Yury I. Miller, Benjamin A. Rissing, Yuqing Huo, Susanna R. Keller, George E. Vandenhoff, Jerry L. Nadler, Thomas M. McIntyre

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Foam cell formation in diabetic patients often occurs in the presence of high insulin and glucose levels. To test whether hyperinsulinemic hyperglycemic conditions affect foam cell differentiation, we examined gene expression, cytokine production, and Akt phosphorylation in human monocyte-derived macrophages incubated with two types of oxidized low density lipoprotein (LDL), minimally modified LDL (mmLDL) and extensively oxidized LDL (OxLDL). Methods and results: Using Affymetrix GeneChip® arrays, we found that several genes directly related to insulin signaling were changed. The insulin receptor and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL, whereas insulin-induced gene I was significantly down-regulated. In hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt phosphorylation and expression of the insulin-regulated aminopeptidase. The level of proinflammatory cytokines, IL-1β, IL-12, and IL-6, and of a 5-lipoxygenase eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE), was also increased. Conclusion: These results suggest that the exposure of macrophages to modified low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects insulin signaling and promotes the release of proinflammatory stimuli, such as cytokines and eicosanoids. These in turn may contribute to the development of insulin resistance.

Original languageEnglish (US)
Article number13
JournalCardiovascular Diabetology
Volume5
DOIs
StatePublished - Jun 20 2006

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Foam Cells
Insulin
Glucose
LDL Lipoproteins
Eicosanoids
Cytokines
Macrophages
Phosphorylation
Arachidonate 5-Lipoxygenase
Aminopeptidases
Glucosephosphate Dehydrogenase
Insulin Receptor
Interleukin-12
Interleukin-1
Genes
Insulin Resistance
Cell Differentiation
Interleukin-6
Gene Expression
oxidized low density lipoprotein

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Shashkin, P. N., Jain, N., Miller, Y. I., Rissing, B. A., Huo, Y., Keller, S. R., ... McIntyre, T. M. (2006). Insulin and glucose play a role in foam cell formation and function. Cardiovascular Diabetology, 5, [13]. https://doi.org/10.1186/1475-2840-5-13

Insulin and glucose play a role in foam cell formation and function. / Shashkin, Pavel N.; Jain, Nitin; Miller, Yury I.; Rissing, Benjamin A.; Huo, Yuqing; Keller, Susanna R.; Vandenhoff, George E.; Nadler, Jerry L.; McIntyre, Thomas M.

In: Cardiovascular Diabetology, Vol. 5, 13, 20.06.2006.

Research output: Contribution to journalArticle

Shashkin, PN, Jain, N, Miller, YI, Rissing, BA, Huo, Y, Keller, SR, Vandenhoff, GE, Nadler, JL & McIntyre, TM 2006, 'Insulin and glucose play a role in foam cell formation and function', Cardiovascular Diabetology, vol. 5, 13. https://doi.org/10.1186/1475-2840-5-13
Shashkin, Pavel N. ; Jain, Nitin ; Miller, Yury I. ; Rissing, Benjamin A. ; Huo, Yuqing ; Keller, Susanna R. ; Vandenhoff, George E. ; Nadler, Jerry L. ; McIntyre, Thomas M. / Insulin and glucose play a role in foam cell formation and function. In: Cardiovascular Diabetology. 2006 ; Vol. 5.
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