Total Parenteral Nutrition Influences Both Endocrine and Exocrine Function of Rat Pancreas

Fan, Bo-Guang; Salehi, Albert; Sternby, Berit; Axelson, Jan; Lundquist, Ingmar; Andrén‐Sandberg, Åke; Ekelund, Mats

doi:10.1097/00006676-199708000-00006

Cited by 28 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of our findings, it has been reported that exposure of neural cells to cytokines upregulates the activity of iNOS and downregulates the activity of cNOS (Minc-Golomb et al 1994). The present results are thus in good agreement with our recent observation in rats subjected to total parenteral nutrition (TPN) for 10 days, where glucosestimulated insulin secretory response was greatly impaired (Fan et al 1997;Salehi et al 2001aSalehi et al , 2001b. Islets isolated from TPN-treated rats showed that induction of iNOS and a strong increase in iNOS activity were accompanied by a concomitant decrease in cNOS activity.…”

Section: Discussionsupporting

confidence: 94%

Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion

Qader

Ekelund

Andersson

et al. 2003

Cell and Tissue Research

Self Cite

View full text Add to dashboard Cite

A high level of nitric oxide (NO) produced by inducible NO synthase (iNOS) is involved in pancreatic beta-cell dysfunction and apoptosis. In the present study, we examined whether iNOS is also expressed in beta cells after induction of acute pancreatitis (AP) in the rat. Pancreatic islets taken from AP animals and incubated for 60 min in the presence of 20.0 mmol/l glucose showed a decreased insulin secretory response to glucose. The basal insulin release at 1.0 mmol/l glucose was also moderately reduced. Experiments on the dynamics of insulin secretion from perfused pancreas revealed an impairment of both first and second phase of glucose-stimulated insulin release after the induction of AP. Confocal microscopy demonstrated that most of the beta cells in pancreas of rat with AP expressed strong immunoreactivity for iNOS. This was further confirmed by biochemical and Western blot analysis that showed a marked increase in iNOS protein expression and enzyme activity concomitant with a modest reduction in the cNOS protein and activity. Although the mechanisms underlying the defective insulin secretory response of beta cells seen during the early stage of AP are complex, the present finding suggests that the expression of iNOS and a marked iNOS-derived NO production in the beta cells may play at least a contributory role in the impairment of beta-cell function.

show abstract

Section: Discussionsupporting

confidence: 94%

Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion

Qader

Ekelund

Andersson

et al. 2003

Cell and Tissue Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Long-term lipid infusion in rats is considered a good model for investigating the effect of increased plasma levels of lipids on ␤-cell function and insulin secretion (8,31,34,36,39). We (36) have previously shown that lipid-infused animals are characterized by hyperlipidemia (FFA, triglycerides, and cholesterol), but at the same time they display normoglycemia, and there is no significant difference in blood glucose levels in these rats compared with freely-fed control rats.…”

Section: Discussionmentioning

confidence: 99%

“…pancreatic islets; insulin secretion; isoforms of nitric oxide synthase; pituitary adenylate cyclase-activating polypeptide 27 THE SOLUTION USED for total parenteral nutrition (TPN) contains a high amount of lipids, which results in increased plasma levels of free fatty acid (FFA), triglycerides, and cholesterol (8,31,34,36). FFA has complex effects on pancreatic ␤-cells and insulin secretion (8,9,25,31,32,34,36,45,51). Hence, FFA acutely stimulates insulin secretion from isolated pancreatic islets (9), whereas long-term incubation (24 h) of islets in the presence of FFAs negatively modulates ␤-cell function and results in a markedly decreased glucose-stimulated release of insulin (51).…”

mentioning

confidence: 99%

“…Hence, FFA acutely stimulates insulin secretion from isolated pancreatic islets (9), whereas long-term incubation (24 h) of islets in the presence of FFAs negatively modulates ␤-cell function and results in a markedly decreased glucose-stimulated release of insulin (51). Indeed, it has been known for a long time that chronic elevation of plasma FFA impairs the insulin-secreting response to glucose in both humans and animals (8,31,32,34,36,45,51), and this hyperlipidemia has been suggested to be closely linked to type 2 diabetes (24). We have previously reported that nutrient-stimulated insulin secretion was markedly disrupted after lipid infusion in rats (8, 31, 34 -36, 39) and that this insulin secretory defect could be reversed by agents stimulating cyclic AMP production (34,35,39).…”

mentioning

confidence: 99%

“…FFA has complex effects on pancreatic ␤-cells and insulin secretion (8,9,25,31,32,34,36,45,51). Hence, FFA acutely stimulates insulin secretion from isolated pancreatic islets (9), whereas long-term incubation (24 h) of islets in the presence of FFAs negatively modulates ␤-cell function and results in a markedly decreased glucose-stimulated release of insulin (51).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Expression of islet inducible nitric oxide synthase and inhibition of glucose-stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27

Qader

Jimenez-Feltström²,

Ekelund³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Qader SS, Jimenez-Feltström J, Ekelund M, Lundquist I, Salehi A. Expression of islet inducible nitric oxide synthase and inhibition of glucose-stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27. Am J Physiol Endocrinol Metab 292: E1447-E1455, 2007. First published January 30, 2007; doi:10.1152/ajpendo.00172.2006.-Chronic exposure of pancreatic islets to elevated plasma lipids (lipotoxicity) can lead to ␤-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase (iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to ␤-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive (nc)NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP-and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in ␤-cells. pancreatic islets; insulin secretion; isoforms of nitric oxide synthase; pituitary adenylate cyclase-activating polypeptide 27 THE SOLUTION USED for total parenteral nutrition (TPN) contains a high amount of lipids, which results in increased plasma levels of free fatty acid (FFA), triglycerides, and cholesterol (8,31,34,36). FFA has complex effects on pancreatic ␤-cells and insulin secretion (8,9,25,31,32,34,36,45,51). Hence, FFA acutely stimulates insulin secretion from isolated pancreatic islets (9), whereas long-term incubation (24 h) of islets in the presence of FFAs negatively modulates ␤-cell function and results in a markedly decreased glucose-stimulated release of insulin (51). Indeed, it has been known for a long time that chronic elevation of plasma FFA impairs the insulin-secreting response to glucose in both humans and animals (8,31,32,34,36,45,51), and this hyperlipidemia has been suggest...

show abstract

Nutritional support during acute pancreatitis

Jensen

Chan

2015

Nutritional Management of Hospitalized Small Animals

View full text Add to dashboard Cite

Total Parenteral Nutrition Influences Both Endocrine and Exocrine Function of Rat Pancreas

Cited by 28 publications

References 0 publications

Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion

Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion

Expression of islet inducible nitric oxide synthase and inhibition of glucose-stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27

Nutritional support during acute pancreatitis

Contact Info

Product

Resources

About