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- Ekelund, Mats, et al.
(author)
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Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose or intralipid challenge.
- 2006
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In: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 22:2006 Apr 22, s. 652-660
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Journal article (peer-reviewed)abstract
- Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and blood samples were drawn for analysis of plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each animal and investigated for the occurrence of iNOS by the use of confocal microscopy, western blot, and high-performance liquid chromatographic analysis. The effect of intravenously infused glucose was then compared with the effect of an intravenous infusion of Intralipid (IL). Results: Plasma insulin levels were markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels were markedly increased in the IVG group, whereas both parameters were decreased in the IL group. No significant differences in plasma insulin, glucagon, or glucose were found between the OG and FF groups. Immunocytochemical (confocal microscopy), western blot, and biochemical (high-performance liquid chromatographic) analyses showed that a sustained increase in plasma level of glucose or free fatty acids by an intravenous infusion of either nutrient for 24 h resulted in a marked expression and activity of iNOS in pancreatic islets. No sign of iNOS expression could, however, be detected in the islets of FF control or OG rats. Conclusion: The data suggest that impaired beta-cell function found after 24 It of an intravenous infusion of glucose or Intralipid might be mediated, at least in part, by the induction of iNOS in pancreatic islets. This may subsequently result in an exclusive production of nitric oxide, which is deleterious for beta-cells. (C) 2006 Elsevier Inc. All rights reserved.
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| 2. |
- Qader, Saleem, et al.
(author)
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Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rats.
- 2005
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In: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 131:Aug 12, s. 82-88
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Journal article (peer-reviewed)abstract
- Background: Ghrelin derives from endocrine cells (A-like cells) in the stomach (mainly the oxyntic mucosa). Its concentration in the circulation increases during fasting and decreases upon re-feeding. This has fostered the notion that the absence of food in the upper gastrointestinal (GI) tract stimulates the secretion of ghrelin. The purpose of the present study was to determine the concentration of ghrelin in serum and oxyntic mucosa after replacing food with intravenous (iv) infusion of nutrients for 8 days using the technique known as total parenteral nutrition (TPN). Materials and methods: Male Sprague-Dawley rats (200-250 g) were given nutrients (lipids, glucose, amino acids, minerals and vitamins) by iv infusion for 8 days during which time they were deprived of food and water; another group was deprived of food for 24-48 h (fasted controls), while fed controls had free access to food and water. Serum ghrelin, gastrin and pancreastatin concentrations were measured together with the ghrelin content of the oxyntic mucosa. Plasma insulin and glucose as well as serum lipid concentrations were also determined. Results: Fasted rats had higher serum ghrelin than TPN rats and fed controls. The oxyntic mucosal ghrelin concentration (and content) was lower in TPN rats than in fasted rats or fed controls. The serum gastrin and pancreastatin concentrations were lower in TPN rats and fasted rats than in fed controls. The plasma insulin concentration was 87 pmol/l +/- 8 (SEM) in TPN rats compared to 101 16 pmol/l in fed controls; it was 26 14 pmol/l in fasted rats. The basal plasma glucose level was 11 +/- 0.6 mmol/l in TPN rats and 12 +/- 0.8 mmol/l in fed controls; it was 7 +/- 0.3 mmol/l in fasted rats. In TPN rats, the serum concentrations of free fatty acids, triglycerides and cholesterol were increased by 100%, 50% and 25%, respectively, compared to fed controls. Fasted rats had higher circulating concentrations of free fatty acids (20%) and lower concentrations of triglycerides (- 40%) than fed controls; fasted rats did not differ from fed controls with respect to serum cholesterol. Conclusion: The circulating ghrelin concentration is high in situations of nutritional deficiency (starvation) and low in situations of nutritional plenty (free access to food or TPN). The actual presence or absence of food in the GI tract seems irrelevant. Circulating insulin and glucose concentrations did not differ much between TPN rats and fed controls, serum lipids, however, were elevated in the TPN rats. We suggest that elevated blood lipid levels contribute to the suppression of circulating ghrelin in rats subjected to TPN for 8 days.
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