Pancreatic pathology in non-insulin dependent diabetes (NIDDM).
NIDDM is a heterogeneous disease and subgroups of NIDDM include MODY (Maturity Onset Diabetes of the Young), Malnutrition-related diabetes (MRDM) and Fibrocalculus pancreatic diabetes (FCPD). Endocrine cell population is relatively unchanged in NIDDM: B-cells are reduced by up to 30% and A-cells increased by 10%. Islet amyloid is found in 96% of subjects occupying up to 80% of the islet associated with a reduction in B-cells. Amyloid formation is unlikely to cause diabetes but progressive accumulation increases the severity of the disease. Islet amyloid is formed from the islet amyloid polypeptide (IAPP), a normal constituent of B-cells, co-secreted with insulin. The causal factors for IAPP fibrillogenesis are unknown but abnormal synthesis or overproduction could be involved: stimulation of B-cell secretion in NIDDM by obesity, hyperglycaemia or suphonylurea therapy may promote amyloidosis and further aggravate islet pathology. A mutation of the glucokinase gene in MODY leads to diminished B-cell secretion but not amyloid formation. Diabetes and mutations of mitochondrial DNA is associated with poorly developed islet structure. Exocrine pancreatic size is reduced and there is evidence of sub-clinical chronic pancreatitis in NIDDM. In MRDM and FCPD, chronic pancreatitis and exocrine necrosis is associated with reduced insulin secretion. Unlike cystic fibrosis where islet amyloid is present in diabetic individuals, amyloid is absent from subjects with FCPD. Pathological changes in the exocrine and endocrine pancreas in NIDDM results from and contributes to the pathophysiology of insulin secretion in NIDDM.
Diabetes Research Laboratories, Radcliffe Infirmary Hospital, Oxford, UK.
A
A
Clark
E J
EJ
de Koning
A T
AT
Hattersley
B C
BC
Hansen
C S
CS
Yajnik
J
J
Poulton
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D004272:DNA, Mitochondrial / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000473:pathology
D000682:Amyloid; D004272:DNA, Mitochondrial; D007328:Insulin; D058228:Islet Amyloid Polypeptide