Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: Interest of a graded arginine supply
ABSTRACT Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion.
Randomized, controlled experimental study.
University research laboratory.
Zucker diabetic fatty rats.
Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n=7) or with graded arginine supply (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10).
Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-α (G: 5.0±1.1 ng/2×10⁶ cells·hr⁻¹; GA: 3.7±0.8 ng/2×10⁶ cells·hr⁻¹; and HP: 1.7±0.6 ng/2×10⁶ cells·hr⁻¹; p<.05 G vs. HP) and nitric oxide (G: 4.5±1.1 ng/2×10⁶ cells·hr⁻¹; GA: 5.1±1.0 ng/2×10⁶ cells·hr⁻¹; and HP: 1.0±0.5 nmol/2×10⁶ cells·hr⁻¹; p<.05 G and GA vs. HP) productions were higher in the G and GA groups compared to the HP group. Macrophages from the G and GA groups exhibited increased arginine consumption.
In diabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill diabetic and obese patients.
SourceAvailable from: ecrossingsmedia.netDiabetes Care 03/2004; 27(2):553-91. DOI:10.2337/diacare.27.2.553 · 8.57 Impact Factor
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ABSTRACT: Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils. Laboratory studies of short-term cultures of neutrophil granulocytes. Healthy subjects. Neutrophils were isolated from peripheral blood and incubated for 1 h in Krebs-Ringer buffer containing 5, 10, or 25 mM glucose, 5 mM glucose with 0, 5, or 20 mM mannitol, or 5 mM glucose with 0, 1, 10, or 100 micro M DHEA. O(2)(-) production was induced by N-formyl-methionyl-leucyl-phenylalanine and measured by the cytochrome c reduction assay. Potential scavenging of O(2)(-) by glucose, mannitol, or DHEA was assessed in a cell free system using the pyrogallol assay. Incubation of neutrophils with glucose dose-dependently reduced O(2)(-) production, which was 50% decreased at 25 mM glucose. Also DHEA reduced the production of O(2)(-) dose-dependently, whereas production rates were unaffected by mannitol. Neither glucose, mannitol, nor DHEA scavenged O(2)(-). High extracellular glucose concentrations acutely reduce O(2)(-) production from activated neutrophils possibly through inhibition of G6PD. If this occurs in vivo, microbial killing by neutrophils may be impaired during acute hyperglycemia, as observed after major surgery, trauma, or severe infection.Intensive Care Medicine 05/2003; 29(4):642-5. DOI:10.1007/s00134-002-1628-4 · 5.54 Impact Factor
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ABSTRACT: This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.Journal of Nutrition 05/2005; 135(4):714-21. · 4.23 Impact Factor