PubMed Health⌕ Search

Biomedical subjects

D Brandhorst

Publications and source records attributed to D Brandhorst.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Graft rejection in experimental xenogenic transplantation of isolated islands of Langerhans of the pig].

Prevention of the occurrence of diabetes-specific vascular complications is the final aim of clinical islet transplantation. Pancreatic islets isolated from adult pigs may be a suitable tissue source to transplant a large number of type 1 diabetic patients. Acute cellular rejection may be finally overcome by clinically applicable protocols for tolerance induction. However, primary nonfunction of the graft, as regularly observed in the porcine islet-to-rat xenotransplantation model, may be an additional problem. In this paper, species-specific inflammatory and immunological mechanisms are discussed which prevent early porcine islet graft function in rats but not in mice.

Adult↗
PubMed1997

Leptin inhibition of insulin secretion from isolated human islets.

Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety, food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic beta-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an "adipo-insular axis" in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas.

Animals↗
PubMed1996

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/di) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1 +/- 1.4 mg/kg/ min; P < 0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4 +/- 0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9 +/- 0.5 mg/kg/min in patients without islet function and 5.3 +/- 0.4 mg/kg/min in patients with islet function) with respect to normals (P < 0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

Islet isolation from the pancreas of large mammals and humans: 10 years of experience.

Despite experience, that has been obtained in the field of islet isolation in large mammals for about the past 20 years, allo- and autotransplantation of both human and porcine islets are still not routine procedures. The reasons for islet isolation and purification associated problems, which prevent a continuous isolation success and regular islet transplantation, can be categorized to variables related to 1) pancreas donor; 2) pancreas procurement; 3) isolation-techniques and 4) purification techniques. The development of porcine and human islet isolation was carried out by the authors since 1986. During this period several techniques for the isolation and purification of human and porcine islets were compared with regard to their influence on islet isolation outcome, integrity of islet morphology, islet in-vitro and in-vivo function: sequential vs continuous digestion-filtration, counterflow elutriation vs neutral density separation, conventional density gradient centrifugation vs Cobe cell separation and discontinuous vs continuous gradient purification. Furthermore, we analysed the influence of donor factors and variables related to organ procurement on islet isolation success. From this experience we concluded that successful porcine islet isolation is possible if islets of adult donors are isolated utilizing the continuous digestion-filtration following distension with UW-solution prior to a neutral density gradient purification on a Cobe. Human islets can be successfully isolated by digestion-filtration and purified utilizing a continuous Ficoll-sodium-diatrizoate gradient on a Cobe when intact pancreata are harvested after a secondary pancreatic warm ischemia time < 20 min from adult donors > 30 years.

Adult↗
PubMed1995

Body mass index of pancreatic donors: a decisive factor for human islet isolation.

Despite improvements in islet isolation techniques, islet transplantation remains unpredictable as a method for reliably rendering human type I diabetic recipients normoglycemic. Advances in immunosuppression to prevent primary nonfunction, to promote engraftment and to prevent rejection should improve success rates. However, factors influencing the isolation process remain incompletely defined. During our experience, the donor's nutritional status as well as other donor characteristics were noted to be associated with islet isolation success. Thus, in this study, we tried to clarify whether the body mass index of the human pancreatic donor affects islet isolation yield and viability. In lean donors we found significantly lower islet yields in comparison with normal and obese donors and a significantly lower islet viability compared to obese donors. Obese donor islets had a significantly higher insulin secretory capacity than lean and normal donor islets. In summary, islet yield and viability were improved selecting pancreata from obese donors associated with a BMI > 24 for islet preparation. We hypothesize that, on the one hand, the increased distribution of fat in pancreata of obese donors possibly can facilitate the release of islets during the collagenase digestion, and, on the other hand, pancreata of obese donors contain more islets than pancreata of lean donors. These data underline the decisive influence of the pancreas donor's body mass index on successful human islet isolation. The body mass index should be noted as a potential predictor of success of islet preparations.

Body Mass Index↗
PubMed1995

Different toxic effects of hydrogen peroxide, nitric oxide, and superoxide on human, pig, and rat islets of Langerhans.

Susceptibility of islet cells to damage by hydrogen peroxide, superoxide, and nitric oxide was determined on islets isolated from humans, pigs, and rats. Islets were incubated for 20 hr at 37 degrees C with different concentrations of hydrogen peroxide, hypoxanthine/xanthine oxidase, or nitroprusside sodium, respectively. Islet cell damage was then measured as trypan blue-uptake. Rat islets showed a higher sensitivity than human or pig islets to damage by reactive oxygen species or nitric oxide. These results indicate that pig islets may be a more suitable model than rat islets to study inflammatory islet cell damage in diabetes and clinical islet transplantation.

Animals↗
PubMed1995

The effects of glucagon-like peptide-I (GLP-I) on hormone secretion from isolated human pancreatic islets.

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone that is now considered as a new therapeutic tool in the treatment of diabetes mellitus. In this study we characterized the effects of GLP-I on peptide hormone release from isolated human pancreatic islets. GLP-I stimulated insulin release in the presence of 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%; 10 mM glucose + 10 nM GLP-I, 222%) but had only a weak insulinotropic effect (128%) at 2.8 mM glucose. Glucagon release was inhibited by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 72%) and by 10 nM GLP-I at 2.8 mM glucose (67%). Somatostatin secretion was increased by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%). GLP-I stimulated somatostatin release in the presence of 2.8 mM glucose (172%). Pancreatic polypeptide (PP) secretion was enhanced by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 236%). GLP-I induced PP release only in the presence of 2.8 mM glucose (184%).

Culture Techniques↗
PubMed1995

[Combined liver-islet transplantation after epigastric exenteration in carcinoma of Vater's ampulla].

A 44 year old female underwent an upper abdominal exenteration because of an adenocarcinoma of the pancreas with liver metastases (T1 N1 M1). Reconstruction was performed by orthotopic liver transplantation and intraportal islet transplantation. Due to initial non function of the first liver graft, a second liver transplantation was performed. Thereafter, the patient received 375,000 islet equivalents of the primary liver donor in addition to 295,400 islet equivalents of another donor. Six months postoperatively, the patient is off insulin except irregular injections of 4-6 units of insulin to protect her from hyperglycemia after lunch. CT scans of the liver do not show any signs of tumor recurrence. Upper abdominal exenteration with consecutive islet transplantation offers a good method of reconstruction after radical surgery in the upper abdomen. The oncological aspects of the procedure have to be further investigated.

Adenocarcinoma↗