glucagon-like-peptide-2 and Hyperplasia

To date, the hormonal factors used in the treatment of patients with short-bowel syndrome have been growth hormone and glucagon-like peptide (GLP)-2. In high-dose growth hormone studies, the effects on wet-weight absorption of approximately 0.7 kg/day have mainly been described in short-bowel syndrome patients with a preserved colon who also received oral rehydration solutions. Treatment with high doses of growth hormone is associated with severe adverse effects in the majority of patients. Low-dose growth hormone increased energy absorption by approximately 1.8 MJ/day in a group of 12 short-bowel syndrome patients (9 with a preserved colon), but it did not affect wet-weight absorption. Growth hormone does not seem to affect either wet-weight or energy absorption in patients with a jejunostomy. GLP-2 and the analogue teduglutide mainly affect wet-weight absorption, resulting in a mean increase in wet-weight absorption of 0.4-0.7 kg/day. The effects on energy absorption are minor at 0.4-0.8 MJ/day. However, these effects are seen in all short-bowel syndrome patients, regardless of anatomy, and the adverse effects are minor. In all studies employing growth hormone or GLP-2, the effects are transient, disappearing when treatments are discontinued. With the need for long-term treatment, adverse effects and safety issues become important. Therefore, it is recommended that treatment is initiated in research settings only and that close monitoring of the long-term effects is a part of the protocol.

Topics: Body Composition; Body Weight; Creatinine; Drug Monitoring; Energy Intake; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Glutamine; Growth Hormone; Humans; Hyperplasia; Intestinal Absorption; Intestinal Mucosa; Intestines; Peptides; Randomized Controlled Trials as Topic; Short Bowel Syndrome; Time Factors

Of the many models of intestinal adaptation, the structural and functional changes seen in the residual small bowel following jejunectomy or ileectomy are the most predictable and best studied. There are three major mechanisms for these adaptive phenomena: changes in i) luminal nutrition, ii) pancreatico-biliary secretions and iii) hormonal factors. Observations in a unique patient with an "enteroglucagon"-secreting tumor of the kidney associated with massive small bowel enlargement, provided the strongest evidence, at that time (>30 y ago), in favor of hormonal factors. When the patient's renal tumor was removed, the markedly increased circulating concentrations of the glucagon-like peptide (now presumed to be GLP-2) returned to normal-as did her intestinal anatomy. Subsequent studies showed that there are increased tissue and plasma enteroglucagon (and recently GLP-2) levels in many animal models of intestinal adaptation. This, and anecdotal evidence from three other case reports, coupled with contemporary studies of GLP-2, strongly suggest that this glucagon-like peptide is a potent, but not the sole, enterotrophin.

Topics: Adaptation, Physiological; Animals; Disease Models, Animal; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; Hyperplasia; Intestinal Mucosa; Intestines; Peptides

We examined the effects of Hachimi-jio-gan (HJ) on the small intestinal function in streptozotocin (STZ)-induced diabetic rats. The rats had free access to pellets containing 1% HJ extract powder for 4 weeks after STZ administration. The intestinal disaccharidase (sucrase and maltase) activity was elevated in STZ-treated rats compared with control rats, whereas it was significantly reduced by HJ administration. This suggested that HJ suppresses or delays monosaccharide production in the small intestinal epithelium. In addition, the intestinal mucosal weights and DNA contents that were significantly increased in the STZ-treated rats were restrained to the control level by HJ treatment. Simultaneously, we examined the changes in the plasma levels of glucagon-like peptide 2 (GLP-2), which is a trophic factor specific for the intestine. The plasma GLP-2 levels significantly increased in the STZ-treated rats, whereas HJ decreased the plasma GLP-2 levels. Thus intestinal mucosal weights and DNA contents correlated with plasma GLP-2 levels in diabetes-associated bowel growth. These results suggest that HJ may normalize or suppress the small intestinal disaccharidase activity and the epithelial cell proliferation mediated by GLP-2 in the animal model rats.

Topics: Animals; Cell Proliferation; Diabetes Mellitus, Experimental; Disaccharidases; Disease Models, Animal; DNA; Drugs, Chinese Herbal; Glucagon-Like Peptide 2; Hyperplasia; Intestinal Mucosa; Intestine, Small; Male; Organ Size; Phytotherapy; Rats; Rats, Wistar; Streptozocin