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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.
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PMID:Transplantation of dispersed pancreatic islet tissue in humans: autografts and allografts. 676 13

Two different methods for isolation of islet of Langerhans on control of metabolic abnormalities of alloxan-induced diabetic rat were tested. Sixty rats were randomly assigned to four experimental groups: GI included 10 non-diabetic control rats, GII included 10 diabetic control rats, without treatment, GIII included 20 diabetic rats (10 inbred and 10 outbred rats) that received islet of Langerhans transplantation (ILT) using islet cells prepared by collagenase, and GIV included 20 diabetic rats (10 inbred and 10 outbred rats) submitted to ILT using islet cells prepared by nonenzymatic method. Clinical and laboratory parameters at beginning and 4, 7, 14, 21 and 30 days of follow-up were recorded. Outbred rats were immunosuppressed with cyclosporin A, diabetes was induced by e.v. alloxan administration, and islet cells were isolated from normal donor Lewis rats and injected into the portal vein. ILT corrected the body weight gain, polyuria, polydipsia, polyphagia, and the high levels of blood and urine glucose in 73.7% of rats treated by enzymatic method and in 64.7% of those ones treated by nonenzymatic method. However, there was no significantly difference between the two methods (P > 0.50). We did not also observe significantly difference between the two methods when ILT was performed either in inbred or outbred rats. We concluded that ILT performed by nonenzymatic method may be an alternative treatment for diabetes due to be less expensive and to have possible advantages in the isolation process.
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PMID:[Islet of Langerhans transplantation. A comparative study of two different methods for isolating islet cells from rat pancreas]. 945 57

The study population in this report by Lin et al. was ob/ob mice that have an inherited genetic deficiency of the appetite-suppressing hormone leptin. These mice develop hyperinsulinemia, insulin resistance, and fatty livers. Compared with their lean littermates and wild-type C57BL-6 mice, ob/ob mice have hepatomegaly. In this study, the authors compared three different groups of adult mice (aged 8-10 wk), including male ob/ob C57BL-6 mice, their lean littermates, and wild-type C57BL-6 mice of the same age and sex. The primary purpose of this study was to test the efficacy of metformin for treatment of fatty liver disease in obese, ob/ob mice that develop hyperinsulinemia or insulin resistance and fatty livers. Metformin therapy was found to eliminate fatty liver disease in this model. The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis. In these experiments, ob/ob mice were divided into three treatment groups. Group 1 consisted of eight mice that were treated with metformin and permitted to consume a nutritiously replete liquid mouse diet ad libitum. Mice in group 2 (n = 8) did not receive metformin but were pair-fed the same volume of liquid diet that the mice in the metformin-treated group had consumed on the previous day. Obese ob/ob mice in group 3 (n = 4) and lean mice received no metformin, as with the mice in group 2, but were permitted to consume the liquid diet ad libitum. Liquid diet was given to facilitate accurate daily comparison of food intake among the various treatment groups. All mice were weighed at the beginning of the study and weekly thereafter until killed and then sera, fat, and liver tissues were collected. Tissues were either fixed in buffered formalin and processed from the deceased mice for histology or snap frozen in liquid nitrogen and stored until RNA and proteins were isolated. The feeding protocol was repeated with a second group of 18 ob/ob mice. After 4 wk, hepatocytes were obtained by in situ liver perfusion with collagenase and assayed for cellular adenosine triphosphate (ATP) content. In each experiment, hepatocytes isolated from 3 mice from each treatment group were suspended in a medium and pooled for subsequent analysis to evaluate cell viability, determine the number of obtained cells, and to assay cellular ATP content. These experiments were repeated using another 3 mice from each treatment group, so that analysis of hepatocytes took place from six ob/ob mice in each feeding group.Hepatic steatosis was decreased significantly only in the metformin-treated group. The authors found that metformin's beneficial effect on the fatty liver disease of mice was not due to its ability to constrain hyperphagia, nor due to decreased caloric ingestion, because the daily caloric intakes of the metformin-treated mice and the pair-fed control mice were virtually identical. These caloric intakes were consistently approximately 20% less than that of another obese control group that was permitted to consume diet ad libitum. The authors also observed no significant effect of metformin on serum glucose concentration from fed, ob/ob mice. Metformin is known to reduce hyperinsulinemia by about 40% in both of these obese hyperinsulinemic and insulin-resistant rodent strains. In conclusion, Lin et al. documented that metformin improves fatty liver disease and reverses hepatomegaly, steatosis, and aminotransferase abnormalities in mice. In addition, the authors suggest that metformin might inhibit dieting-induced redistribution of lipid from the liver to adipose tissue depots. In summary, this study identifies a potential treatment for fatty liver disease in humans.
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PMID:Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. 1449 93