sincalide and Nutrition-Disorders

Severe undernutrition has been associated with reduced secretions of gastric acid and pancreatic enzymes. This may be the result of an impaired gut mucosal response to food and primary gastric parietal and pancreatic acinar cell secretory dysfunction as a consequence of the poor nutritional state. To investigate the relative contributions of these factors, severely undernourished patients underwent enteral-meal-stimulated (ES; n = 7) or intravenous hormone (pentagastrin and cholecystokinin-8)-stimulated (HS; n = 12) gastric acid and pancreatic enzyme secretion before and after a period of nutritional support. Results were evaluated in comparison with normal healthy control subjects (ES = 7, HS = 10). In the control subjects, enteral-meal and cholecystokinin-8 stimulation resulted in similar outputs of the pancreatic enzymes amylase (2213 versus 2305 U/h), lipase (84.93 versus 118.6 U/h), and trypsin (498.9 versus 341.4 U/h), whereas acid output was significantly lower in the ES group (10.90 versus 25.53 mEq/h; P < 0.01). Compared with controls, malnourished groups had significantly reduced secretions of amylase (ES = 870.1 U/h, HS = 686.5 U/h; P < 0.02), lipase (ES = 30.68 U/h, HS = 25.96 U/h; P < 0.02), and trypsin (ES = 175.6 U/h, HS = 109.3 U/h; P < 0.01). The response to enteral-meal or CCK-8 stimulation was comparable. Gastric acid was similarly reduced in the undernourished patients (ES = 4.39 mEq/h, HS = 5.04 mEq/h; P < 0.01). After refeeding, secretion of amylase (ES = 2351 U/h, HS = 2228 U/h) and lipase (ES = 58.83 U/h, HS = 84.91 U/h) improved to levels not significantly different from controls, whereas trypsin (ES = 226.4 U/h, HS = 213.1 U/h; P < 0.03) and acid secretion (ES = 3.52 mEq/h, HS = 11.85 mEq/h; P < 0.01) remained significantly impaired. Severe undernutrition was associated with primary gastric parietal and pancreatic acinar cell dysfunction, which, at least in the case of pancreatic enzymes, appeared to be the determining factor controlling secretion in these patients.

Topics: Adult; Case-Control Studies; Enteral Nutrition; Gastric Acid; Humans; Intestinal Absorption; Intestinal Mucosa; Nutrition Disorders; Nutritional Support; Pancreas; Pentagastrin; Sincalide

Perinatal malnutrition and growth retardation at birth are suggested to be important risk factors for the development of overweight and syndrome X in later life. Underlying mechanisms are unknown. Body weight and food intake are regulated, e.g. by hypothalamic neuropeptidergic systems which are thought to be highly vulnerable to persisting malorganization due to perinatal malnutrition. To investigate possible consequences for hypothalamic cholecystokinin-8S (CCK-8S) in the offspring, pregnant Wistar rats were fed an 8% protein diet during pregnancy and lactation (low-protein group; LP) while control mothers (CO) received a 17% protein isocaloric standard diet. LP offspring displayed underweight at birth (P < 0.05) and during suckling (P < 0.001), while leptin levels were not altered. At weaning, under basal conditions CCK-8S was decreased in LP offspring in the paraventricular hypothalamic nucleus and arcuate hypothalamic nucleus (P < 0.05), as well as in the dorsomedial hypothalamic nucleus, lateral hypothalamic area and ventromedial hypothalamic nucleus (P < 0.01). In summary, these data indicate (1) an inhibition of the satiety peptide CCK-8S in main regulators of body weight and food intake in low-protein malnourished newborn rats; (2) no direct relationship of hypothalamic CCK-8S to circulating leptin at this age; and (3) no neurochemical signs of hypothalamic CCKergic dysregulation in this animal model at the age of weaning.

Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Dietary Proteins; Disease Models, Animal; Eating; Female; Hypothalamus; Insulin Resistance; Male; Maternal-Fetal Exchange; Nutrition Disorders; Obesity; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Sincalide

The chronically reserpine-treated rat, an experimental model for cystic fibrosis, exhibits generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. Although chronic reserpine treatment induces malnutrition by decreasing food consumption and growth, the effects of this malnutrition per se on the exocrine pancreas have not been considered. In this study, the effects of chronic reserpine treatment and malnutrition on the exocrine pancreas were determined using pair-fed controls. Male, Sprague-Dawley rats were treated daily subcutaneously for 5 to 7 days with: no injection (control), 1.0 ml/kg vehicle or sham (control-sham, pair fed-sham), or 0.5 mg/kg reserpine (chronically reserpine-treated). Both chronic reserpine-treatment and pair-feeding significantly decreased food consumption (40%), body weight (51 and 59%), total pancreatic amylase (49 and 56%) and specific amylase activity (62 and 61%), pancreatic protein (65 and 75%), and pancreatic weights (62 and 65%) compared to controls. These decreases, however, were comparable between the chronically reserpine-treated and pair fed-sham rats. In contrast, the secretory response to the biologically active cholecystokinin analog cholecystokinin octapeptide was significantly attenuated in isolated pancreatic acini prepared from reserpine-treated rats compared to that from either control or pair-fed sham rats. Malnutrition decreased pancreatic amylase activity and protein comparably to reserpine treatment, but only partially attenuated the secretory response to cholecystokinin octapeptide. Based on the results of this study, pair-fed controls should be used to distinguish between the effects of reserpine alone and the induced malnutrition on pancreatic exocrine function in studies of this experimental model of cystic fibrosis.

Topics: Amylases; Animals; Body Weight; Cystic Fibrosis; Disease Models, Animal; Eating; Lipase; Male; Nutrition Disorders; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Reserpine; Sincalide