Branched-Chain Amino Acid-Enriched Diet: Effects on Insulin Secretion and Cellular Immune Aggression

Abstract

Several reports have demonstrated that high-protein diets may have beneficial effects on experimental models of diabetes and have raised the possibility that branched-chain amino acids could play a role in these protective effects. We investigated the effect of a normoproteic, branched-chain amino acid-enriched diet (experimental diet) on insulin secretion from C57BL/6N mice transferred with splenocytes from diabetic syngeneic donors. Mice previously fed with the experimental or control diet received three intraperitoneal injections, every other day, of 5 x 107 viable mononuclear splenocytes obtained from control or diabetic donors. Results showed that mice fed with the experimental diet and transferred with "diabetic" splenocytes presented: i) normoglycemia, and (ii) significantly higher levels in both phases of glucose-induced insulin secretion and normal values of arginine-glucose-induced insulin secretion. To evaluate the in vitro cellular immune aggression, dispersed mouse islet cells were co-cultured with splenocytes from syngeneic diabetic mice. First, dispersed islet cells from mice on the experimental or control diet were co-cultured with splenocytes from control or diabetic mice on a commercial diet. In the presence of "diabetic splenocytes, dispersed islet cells from mice on the experimental diet presented a significantly lower in vitro cellular immune aggression. On the other hand, "diabetic" splenocytes from mice fed with the experimental diet produced a significantly reduced cellular immune aggression on dispersed islet cells. Our results showed that feeding branched-chain amino acids increased the capacity of beta cells to withstand a functional assault and diminished the extent of in vitro cellular immune aggression.

Acetyl-L-Carnitine and Nicotinamide for Prevention of Type 1 Diabetes. I-Literature Review which Gave Support to the Treatment. II-Case Report, Evaluation of Five Years Treatment

“…Specifically, an increase in succinate or succinic acid monomethyl ester stimulated proinsulin biosynthesis in ß-cells. The increment in energy, insulin, IGF-I, amino acid synthesis and the availability of branched chain amino acid are basic conditions for ß-cells regeneration [75][76][77].…”

Inhibition of Nitric Oxide Generation in Mononuclear Splenocytes from Multiple-Low-Dose-Streptozotocin Diabetic Mice

“…Mononuclear splenocytes (MS) were aseptically isolated by shredding the spleens with steel wire mesh with sterile NaCl 154 mmol/l solution (Buschard et al, 1977;Karabatas et al, 2000 and. MS were obtained using a Lymphoprep TM gradient (Nycomed Pharma, Norway) and then washed three times with sterile saline solution.…”

“…Islets of Langerhans from mld-SZ mice or from mice transferred with MS were perifused (25-40 islets per chamber) as described previously (Karabatas et al, 2000 and. Krebs-Ringer-bicarbonate buffer was utilized as the perifusion buffer, and was supplemented with 1% (w/v) dextran 70 (Sigma, St. Louis, Missouri, USA) and 3.3 mmol/l glucose.…”

“…Supernatants were withdrawn after 5 min and rapidly frozen for insulin determinations. Islet cells function was expressed as the insulin secretion (µU/5000 cells) during 5-min incubation period in the presence of basal or stimulatory medium (Boitard et al, 1982;Karabatas et al, 1996 and2000). Results of cellular immune aggression test were reproducible with a 3.89% inter-assay and 4.20% intra-assay coefficient of variation (CV), both for ctr.MS or diab.MS.…”

“…In these mice, a diminished insulin secretion is present 15 days after the transfer procedure, and a preferential trapping of transferred diab.MS in islets of recipient mice was observed. Diab.MS obtained as early as day 4, were able to impair insulin secretion in transferred normal syngeneic recipients (Buschard et al, 1977;Pastorale et al, 2002;Karabatas et al, 2000 and.…”