Islet beta-cell area and hormone expression are unaltered in Huntington's disease.
Neurodegenerative disorders are often associated with metabolic alterations. This has received little attention, but might be clinically important because it can contribute to symptoms and influence the course of the disease. Patients with Huntington's disease (HD) exhibit increased incidence of diabetes mellitus (DM). This is replicated in mouse models of HD, e.g., the R6/2 mouse, in which DM is primarily caused by a deficiency of beta-cells with impaired insulin secretion. Pancreatic tissue from HD patients has previously not been studied and, thus, the pathogenesis of DM in HD is unclear. To address this issue, we examined pancreatic tissue sections from HD patients at different disease stages. We found that the pattern of insulin immunostaining, levels of insulin transcripts and islet beta-cell area were similar in HD patients and controls. Further, there was no sign of amyloid deposition in islets from HD patients. Thus, our data show that pancreatic islets in HD patients appear histologically normal. Functional studies of HD patients with respect to insulin secretion and islet function are required to elucidate the pathogenesis of DM in HD. This may lead to a better understanding of HD and provide novel therapeutic targets for symptomatic treatment in HD.
Bacos
Karl
K
Unit of Molecular Metabolism, Department of Experimental Medical Science, Lund University, CRC 91-11, 205 02 Malmö, Sweden. karl.bacos@med.lu.se
Björkqvist
Maria
M
Petersén
Asa
A
Luts
Lena
L
Maat-Schieman
Marion L C
ML
Roos
Raymund A C
RA
Sundler
Frank
F
Brundin
Patrik
P
Mulder
Hindrik
H
Wierup
Nils
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003224:Congo Red / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007120:Immunochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D007328:Insulin; D036361:Peptide Hormones; D003224:Congo Red