We therefore set out to determine whether serum concentrations of C5, C8 and TTR can be used as biomarkers for patients with HNF4A-MODY and HNF1A-MODY.
Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when compared with control subjects (P < 0.02) as well as with HNF-4alpha/MODY1 subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia is the primary cause of decreased serum apoM protein concentrations.
Here we show that two dominant-negative mutants of hepatocyte nuclear factor-1alpha (HNF-1alpha), P447L and P519L, occurring in maturity onset diabetes of the young (MODY3) patients, exhibit paradoxically stronger interactions than the wild-type protein with either CBP or P/CAF.
Plasma glucagon concentrations were similar at basal glycemia (73+/-6, 69+/-5 and 69+/-7 ng/l) and reached peak values of 88+/-9, 88+/-11 and 89+/-7 ng/l at a glycemia of 3.6 mmol/l in MODY3 patients, patients with NIDDM and controls respectively (NS).
Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects.
Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations.
Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis.
Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction.
The amount of insulin secreted during a 10mmol/l glucose clamp was decreased in affected MODY3 subjects (171+/-78pmol/kg BW) and MODY2 subjects (302+/-104pmol/kg BW) as compared with control subjects (770+/-199pmol/kg BW; P=0.0001).
Recently, hepatocyte nuclear factor-1alpha(HNF-1alpha, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3).
Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form.
Here we show that subjects with the MODY3-form of NIDDM have mutations in the gene encoding hepatocyte nuclear factor-1alpha (HNF-1alpha, which is encoded by the gene TCF1).
Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when compared with control subjects (P < 0.02) as well as with HNF-4alpha/MODY1 subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia is the primary cause of decreased serum apoM protein concentrations.
Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form.