Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass.

BACKGROUND: Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. OBJECTIVE: To study the effects of laparoscopic RYGB on enteroendocrine cells. SETTING: University-affiliated, high-volume bariatric surgery center. METHODS: Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. RESULTS: In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. CONCLUSIONS: RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins.

Genetics of gene expression and its effect on disease.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

Clinical study on gastrointestinal stromal tumors (GIST) in Iceland, 1990-2003.

This is a whole population-based study on clinical symptoms, surgical treatment, and outcome of GIST. All mesenchymal tumors in the digestive tract diagnosed from 1990 to 2003 were identified. All reports were reviewed, all tumors were stained with antibodies to c-kit, and the diagnosis of GIST was confirmed. Clinical, pathological, treatment, and outcome data were analyzed. The study included 53 patients with GIST. The mean age at diagnosis was 65.8+/-13.6 years (SD). Tumor distribution included 62% in the upper, 32% in the middle, and 6% in the lower digestive tract. Mean tumor size was 4.9+/-4.4 cm (SD). Gastrointestinal (GI) bleeding was the main symptom in 53% (20/38) of symptomatic cases; most presented with acute gastrointestinal bleeding. Complete surgical resection was performed in 87% (46/53) of patients. Eight of the 53 tumors (15.1%) metastasized, 7 of which were nongastric. The disease-specific death rate at 5 years was 85%, and 5-year survival after complete resection was 64.1%. We conclude that GISTs are often found incidentally but GI bleeding is the most common presentation. Five-year survival is better than previously reported and gastric GIST seems to be more benign than nongastric. GIST seems to metastasize mainly intra-abdominally.

Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study.

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population-based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990-2003 were evaluated with an immunohistochemical panel including staining for c-kit. The age-adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty-seven of the mesenchymal gastrointestinal tumors were positive for c-kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high-risk category while half of the nongastric tumors (11 of 22) fall into this high-risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high-risk category is 46%. The negative predictive value of low- and very-low-risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population-based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs.

Hormonal changes related to reduced renal blood flow and low urine output under prolonged increased intra-abdominal pressure in pigs.

OBJECTIVE: To investigate effects of prolonged increased intra-abdominal pressure (IAP) on diuresis, renal blood flow, and hormones that influence renal function, in particular endothelin. DESIGN: Experimental study. SETTING: Haukeland University Hospital, Norway. ANIMALS: 21 domestic pigs. METHODS: The TAP was maintained at normal (n = 7) or at 20 mmHg (n = 7) or 30 mmHg (n = 7) for three hours. MAIN OUTCOME MEASURES: Urine output, renal venous pressure, renal artery blood flow (transit-time flowmetry), renal cortex blood flow (microspheres), and renin, aldosterone, atrial natriuretic factor (ANF), adrenaline, noradrenaline, cortisol, and endothelin-1 (ET-1) in renal venous blood. RESULTS: An IAP of 20 mmHg was followed by no significant changes in the variables studied. An IAP of 30mmHg was associated with anuria, considerably reduced renal blood flow and increased renal vascular resistance. The renin activity and the blood concentrations of ET-1, aldosterone, noradrenaline, adrenaline, and cortisol increased during the three hours that IAP was at 30 mmHg. CONCLUSION: An IAP of 20 mmHg did not influence renal haemodynamics or diuresis. The low renal blood flow observed at an IAP of 30 mmHg probably results from reduced arteriovenous pressure difference and vasoconstriction. Increased concentrations of endothelin, angiotensin II, and noradrenaline may account for the vasoconstriction. The anuria can be explained by low renal blood flow and increased reabsorption of sodium in renal tubules caused by aldosterone.