Effects of intravenous glucose and lipids on innate immune cell activation in healthy, obese, and type 2 diabetic subjects

• Published in: Physiological reports Vol. 3; no. 2; pp. e12249 - n/a
• Main Authors: Horvath, Peter, Oliver, Stacy R., Zaldivar, Frank P., Radom‐Aizik, Shlomit, Galassetti, Pietro R.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-02-2015; BlackWell Publishing Ltd
• Subjects: Age; Arteriosclerosis; Atherosclerosis; Carbohydrates; Cardiovascular disease; Cardiovascular diseases; CCR2 protein; CD11b antigen; CD14 antigen; CD16 antigen; Cell activation; Cell surface; Chemokines; Cytokines; Dextrose; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diapedesis; Endothelium; Flow cytometry; Gene expression; Glucose; granulocytes; Hyperglycemia; Hyperlipidemia; Inflammation; Insulin resistance; L-selectin; Leukocytes (granulocytic); Lipids; Monocyte chemoattractant protein 1; monocytes; Neutrophils; NF-κB protein; Obesity; Original Research; Physiology; Smooth muscle; Studies; Surface markers; granulocytes; monocytes; lipids; Glucose
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.12249

Atherosclerosis/cardiovascular disease are major causes of morbidity/mortality in obesity and type 2 diabetes (T2D), and have been associated with activation of innate immune cells, their diapedesis to the arterial intima and formation of the atherosclerotic plaque. While in obesity/T2D immune cell activation likely depends on dysregulated metabolism, the interaction between individual metabolic factors typical of these conditions (hyperglycemia, hyperlipidemia), innate immune cell activation, and the progression of atherosclerosis remains unclear. We, therefore, measured by flow cytometry cell surface expression of CD11b, CD14, CD16, CD62L, and CD66b, known markers of granulocyte (Gc) and monocyte (Mc) activation, in five healthy, five obese, and five T2D subjects, during 4‐h i.v. infusions of 20% dextrose (raising blood sugar levels to ~220 mg/dL), 20% Intralipid (raising trygliceride levels to ~6 mmol/L), or a combination of the two. We hypothesized that both glucose and lipids would increase Gc/Mc surface marker expression, and simultaneous infusion would have an additive or synergistic effect. Surprisingly, though, infusion of glucose alone had little effect, while lipids, alone or combined with glucose, significantly increased expression of several markers (such as CD11b in Gc and Mc, and CD66 b in GC) within 60–90 min. Less pronounced increases in systemic inflammatory cytokines also occurred in obese and T2D subject, with no acute changes in gene expression of the the proinflammatory genes NFκB and CCR2. Our results suggest that lipids may be stronger acute contributors to innate cell activation than acute hyperglycemia per se, possibly helping shape more effective preventive dietary guidelines in T2D.
e12249
The effects of rapid increases in plasma glucose and lipids (obtained via i.v. infusions), on leukocyte expression of inflammatory surface markers, and systemic cytokine concentrations were measured in healthy, obese, and type 2 diabetic subjects. After 30–60 min of hyperlipidemia, either induced alone or in combination with hyperglycemia, several key neutrophil and monocyte surface markers were significantly increased; while hyperglycemia alone, even if prolonged for 4 h, did not induce measurable changes.