Dietary effects on insulin and nutrient metabolism in mesenteric lymph node cells, splenocytes, and pancreatic islets of BB rats

The present studies were performed to determine if a protective diet has di fferent effects on the metabolic activity or function of islet cells, as we ll as the metabolic activity of mesenteric lymph node (MLN) cells and splee n cells, from BioBreeding (BB) rats. Diabetes-prone BB (BBdp) rats and cont rol non-diabetes-prone BB (BBc) rats were fed for about 20 days either a ma inly plant-based diabetogenic diet, NIH-07 (NIH). or a protective semipurif ied diet with hydrolyzed casein (HC) as the amino acid source. At 6 to 8 we eks of age, BBdp rats had high plasma D-glucose and low insulin concentrati ons, low insulin content, and low metabolic and secretory responses to D-gl ucose in isolated pancreatic islets. Islet metabolism, as measured by accum ulation of C-14-acidic metabolites, amino acids, and the ratio of D-[U-C-14 ]glucose oxidation and D-[5-H-3]glucose utilization was increased in contro l rats fed HC (P < .05); a similar trend in BBdp rats was not significant. Feeding the HC diet increased islet insulin content (P < .01) by 13% in BBd p and 23% in BBc rats; other metabolic and hormonal variables were unaffect ed. Compared with BBc rats, BBdp rats displayed higher rates of L-[U-C-14]g lutamine oxidation, D-[5-H-3]glucose utilization, and D-[U-C-14]glucose oxi dation in MLN cells, but not in splenocytes. There was a dramatic decrease of L-[U-C-14]glutamine oxidation in MLN cells from BBc and BBdp rats fed HC . Glycolysis was decreased in control rats. We conclude that the protection afforded by feeding BBdp rats a HC diet is associated with increased insul in in target beta cells and downregulation of metabolic activity in gut-ass ociated MLN cells. Metabolic activity in splenocytes, cells representative of the systemic immune system, was less affected. These data suggest that d iet-induced metabolic changes occur in the islets and nearby cells of the g ut immune system in the period before classic insulitis. Changes in the isl ets were smaller in comparison to the dramatic remodeling of nutrient catab olism in MLN cells. MLN downregulation may reflect baseline metabolic activ ity in the absence of diabetogenic (or other) food antigens and further hig hlights an important interaction between diabetogenic food antigens and the gut immune tissues. Copyright (C) 2000 by W.B. Saunders Company.