Islet amyloid polypeptide (IAPP) and pro-IAPP immunoreactivity in human islets of Langerhans.

Islet amyloid polypeptide (IAPP) is a 37-amino-acid putative hormone which is expressed by islet B-cells and most probably is co-released with insulin. IAPP is synthesized as an 89-amino-acid prepropeptide in which IAPP is flanked by two short peptides. The two short peptides are ultimately cleaved off at basic residues. In the present study, we used antisera to three different synthetic peptides corresponding to positions 18-30, 40-50 and 53-62 of prepro-IAPP. The two latter peptides fall within the mature IAPP molecule while the first peptide corresponds to the N-terminal flanking peptide. We demonstrate that normal B-cells and islet amyloid both react immunohistochemically with all of these antisera. Using the immunogold labelling technique, we also demonstrate electron microscopically that both the IAPP immunoreactivity and the pro1-IAPP immunoreactivity in amyloid deposits are confined to the amyloid fibrils per se. These data indicate that not only mature IAPP but also the N-terminal flanking peptide is present in islet amyloid deposits. It remains to be shown if the propeptide segments are involved in the pathogenesis of these amyloid depositions.

The relation between nutritional state and quality of life in surgical patients.

OBJECTIVE: To explore the relationship between nutritional status and quality of life in a group of patients in a surgical department. DESIGN: Prospective open study. SETTINGS: Department of Surgery, University Hospital, Linköping, Sweden. SUBJECTS: The patients (n = 199) included 89 females and 110 males, mean age 59 years. INTERVENTIONS: The nutritional status was assessed by the percentage weight loss (% WL), weight index (WI), arm muscle circumference (AMC), triceps skin fold thickness (TSF), serum-albumin (Alb) and serum-prealbumin (p-Alb) concentration. Malnutrition was classified as three or more abnormal values and the overall frequency was 35%. The quality of life was assessed by a self-administered rating form with a life-domain rating part and a well-being rating part. In the current statistical analysis, the nutritional status and its different nutritional markers were tested for significant associations with the life-domain ratings (n = 7) and wellbeing scales (n = 11). RESULTS: There were significant relations between malnutrition according to nutritional assessment (p < 0.001), % WL (p < 0.005-0.001), Alb (p < 0.05-0.001), p-Alb (p < 0.01-0.001) and quality of life in all life domains except for the social network sphere. The anthropometric variables AMC and TSF showed no association with life domain ratings. As to the wellbeing ratings, an even stronger and more consistent relation were seen between a malnourished state (p < 0.01-0.001), % WL (p < 0.01-0.001), WI (p < 0.01-0.001), Alb (p < 0.01-0.001) and p-Alb (p < 0.05-0.001). AMC and TSF were not linked to the wellbeing ratings. CONCLUSIONS: In summary, there was a close association between malnutrition and impaired quality of life.

Islet amyloid polypeptide: demonstration of mRNA in human pancreatic islets by in situ hybridization in islets with and without amyloid deposits.

Islet amyloid polypeptide which is normally coexpressed with insulin in beta cells, forms amyloid deposits especially in islets of Type 2 (non-insulin-dependent) diabetic subjects. Occurrence of islet amyloid is paradoxically associated with loss of islet amyloid polypeptide immunoreactivity in beta cells. The present study was undertaken to examine whether the islet amyloid polypeptide gene is expressed in islets with decreased islet amyloid polypeptide immunoreactivity. Pancreatic tissue from 14 patients, 7 with Type 2 diabetes and 7 non-diabetic, were obtained at autopsy or surgery and studied for islet amyloid polypeptide expression by in situ hybridization and for presence of insulin and islet amyloid polypeptide by immunohistochemistry. Six of the specimens from the diabetic and three of those from the non-diabetic patients had varying degrees of islet amyloid polypeptide-derived islet amyloid. Amyloid deposits were associated with decreased numbers of beta cells with islet amyloid polypeptide immunoreactivity despite an apparent normal frequency of insulin-containing cells. This discrepancy might reflect an alteration in islet amyloid polypeptide production or processing at a transcriptional or post-transcriptional level. In contrast to the varying immunohistochemical patterns, islets of all categories showed strong labelling using an islet amyloid polypeptide probe for in situ hybridization. It is concluded that islet amyloid polypeptide production is not altered at the transcriptional level. The following possibilities remain: (1) islet amyloid polypeptide production may be altered at a post-transcriptional level or (2) that islet amyloid polypeptide production is normal but the reduced immunoreactivity of the cells reflects a reduced storage of IAPP in secretory granules.(ABSTRACT TRUNCATED AT 250 WORDS)