Cellular apoptosis induced by hyperglycemia occurs in many vascular cells and is critical to initiate diabetic pathologies. In the retina, pericyte apoptosis, the most specific vascular pathology attributed to hyperglycemia, is linked to the loss of PDGF actions due to unknown mechanisms. Our study demonstrated that hyperglycemia persistently activated PKCδ and p38α MAPK to increase the expression of a novel target, SHP-1, leading to PDGF receptor-β dephosphorylation and actions, and increased pericyte apoptosis, independent of NF-κB. These findings were also observed in diabetic mouse retinas, which were not reversed by achieving normoglycemia with insulin. Unlike diabetic controls, diabetic Prkcd−/− mice did not exhibit p38α MAPK/SHP-1 activation, PDGF resistance or acellular capillaries. Since PKCδ/p38α MAPK/SHP-1 activation are also induced in the brain pericytes and renal cortex by diabetes, these findings have elucidated a new pathway by which hyperglycemia can induce PDGF resistance and increase vascular cell apoptosis to cause diabetic vascular complications.

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1. We established a new animal model of metabolic syndrome, SHRSP fatty (fa/fa) rats, by crossing stroke-prone spontaneously hypertensive rats of the Izumo strain (SHRSP/Izm) to Zucker fatty (ZF) (fa/fa) rats. 2. The SHRSP fatty (fa/fa) rats have a missense mutation of the leptin receptor gene and plasma leptin concentrations are augmented. The SHRSP fatty (fa/fa) rats develop obesity and hypertension simultaneously. 3. Plasma metabolic parameters, including glucose, insulin and total cholesterol and triglyceride levels, were markedly elevated in SHRSP fatty (fa/fa) rats compared with SHRSP/Izm rats. Plasma triglyceride concentrations in SHRSP fatty (fa/fa) rats were significantly elevated compared with those in ZF (fa/fa) rats. The weight of adipose tissues in SHRSP fatty (fa/fa) rats was greater than that of SHRSP/Izm rats. The phenotype of SHRSP fatty (fa/fa) rats is similar to that of human metabolic syndrome.

1. Recent studies have identified potential beneficial effects of eating nuts, most of which have substantial amounts of monounsaturated fatty acids (MUFA). Macadamia nuts consist of 75% fat by weight, 80% of which is MUFA (palmitoleic acid). 2. To examine variations in serum lipid levels in response to a high-MUFA diet based on macadamia nuts, 3 week interventions of macadamia nuts, coconuts and butter were determined in young, healthy Japanese female students. 3. After 3 weeks intervention, serum concentrations of total cholesterol and low-density lipoprotein-cholesterol were significantly decreased in the macadamia nut and coconut diets and bodyweight and body mass index were decreased in the group fed macadamia nuts, although there were no statistically significant changes in the group fed butter.