Elevated free fatty acids (FFAs) contribute to the development of insulin resistance, type 2 diabetes mellitus (T2DM), and may be atherogenic. We tested the relationship among lipid-induced insulin resistance, endothelial dysfunction, and monocyte capacity to form foam cells through scavenger receptor A (SRA) and CD36. Ten healthy subjects underwent 24-h infusion of Intralipid/heparin and saline (0.5 ml/min) on two separate occasions followed by brachial artery reactivity testing and a euglycemic hyperinsulinemic (80 mU/(kg·min)) clamp study to determine insulin sensitivity. Isolation of blood monocytes was performed 24 h after infusion. Surface expression and function of CD36 and SRA to take up oxidized low-density lipoprotein (oxLDL) was determined by flow cytometry and quantitative confocal imaging. Lipid infusion resulted in a twofold increase in serum FFA levels, reduced whole-body glucose disposal by ~20% (P < 0.05), and possibly impaired endothelial-dependent vasodilation (P = 0.1). Blood monocytes obtained during lipid infusion demonstrated a ~25% increase in cell surface expression of CD36 (P < 0.05) but no change in SRA expression. Enhanced CD36 expression was associated with a 50% increase in internalization of oxLDL (P < 0.05). The increase in CD36 surface expression during lipid infusion correlated inversely with glucose disposal (P < 0.05) and not with FFA levels or brachial artery dilation. These data support a role for FFAs in induction of insulin resistance and provide a link to atherogenic mechanisms mediated by expression of scavenger receptor CD36.
Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are rare. In this largest case series reported, we describe the clinical features, treatment and outcome of 5 patients. Over a 6-year period (2000-2006), we treated 5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC was diagnosed a median of 11 years prior to diagnosis of MP (range 0-27 years). Four patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the other two had deficiency of at least ACTH and gonadotropin axes. Elevated prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with suprasellar extension and chiasmal compression in all; prominent vascular flow voids were seen in 2. Three patients underwent transsphenoidal surgery and radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow up 6-46 months); 1 patient died due to systemic metastases at 12 months. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction compared to those from other primaries, whereas DI is less common. MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of sella and presence of vascular flow voids. Combined treatment using decompressive surgery and stereotactic radiotherapy may result in better outcomes.
An 89-year-old man was admitted with frequent, severe hypoglycemic episodes presenting with neuroglycopenic symptoms. About 2 months before admission, he started experiencing recurrent episodes of confusion, seizures, loss of consciousness, and falls. These episodes were not preceded by adrenergic symptoms and could occur at any time, but most occurred within a few hours after meals. Blood glucose (BG) level of 30 mg/dL (1.6 mmol/L) was recorded by paramedics on two occasions, which improved after bolus injections of 50% dextrose.
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