scholarly journals GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1α Mutation Carriers

Diabetes ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1989-2002 ◽  
Author(s):  
Alexander S. Christensen ◽  
Sofie Hædersdal ◽  
Heidi Storgaard ◽  
Kathrine Rose ◽  
Nina L. Hansen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mutation Carriers ◽  
Hepatocyte Nuclear Factor 1Α

Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1α mutation carriers

2005 ◽  
Vol 22 (4) ◽  
pp. 406-409 ◽  
Author(s):  
J. V. Sagen ◽  
E. R. Pearson ◽  
A. Johansen ◽  
G. Spyer ◽  
O. Søvik ◽  
...  
Keyword(s):  
Insulin Response ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mutation Carriers ◽  
Hepatocyte Nuclear Factor 1Α

scholarly journals GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1-Alpha Mutation Carriers

2020 ◽  
Author(s):  
Ada Admin ◽  
Alexander S. Christensen ◽  
Sofie Hædersdal ◽  
Heidi Storgaard ◽  
Kathrine Rose ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucagon Secretion ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mutation Carriers ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Nuclear Factor 1 ◽  
Double Blinded ◽  
Insulinotropic Peptide

Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1-alpha (HNF1A)-diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like-peptide 1 (GLP-1), are characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A-diabetes is currently unknown. To investigate this, ten <i>HNF1A </i>mutation carriers and ten non-diabetic controls were recruited for a double-blinded, placebo-controlled, crossover study including six experimental days in a randomized order involving 2h euglycemic-hyperglycemic clamps with co-administration of 1) SU (glimepiride 1 mg) or placebo, combined with 2) infusions of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or saline (NaCl). In <i>HNF1A </i>mutation carriers we observed: 1) hypoinsulinemia, 2) insulinotropic effects of both GIP and GLP-1, 3) <a>additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP1, respectively, </a>and 4) increased fasting and arginine-induced glucagon levels compared to non-diabetic controls. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A-diabetes via potentiation of glucose-stimulated insulin secretion.

scholarly journals GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1-Alpha Mutation Carriers

2020 ◽  
Author(s):  
Ada Admin ◽  
Alexander S. Christensen ◽  
Sofie Hædersdal ◽  
Heidi Storgaard ◽  
Kathrine Rose ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucagon Secretion ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mutation Carriers ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Nuclear Factor 1 ◽  
Double Blinded ◽  
Insulinotropic Peptide

Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1-alpha (HNF1A)-diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like-peptide 1 (GLP-1), are characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A-diabetes is currently unknown. To investigate this, ten <i>HNF1A </i>mutation carriers and ten non-diabetic controls were recruited for a double-blinded, placebo-controlled, crossover study including six experimental days in a randomized order involving 2h euglycemic-hyperglycemic clamps with co-administration of 1) SU (glimepiride 1 mg) or placebo, combined with 2) infusions of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or saline (NaCl). In <i>HNF1A </i>mutation carriers we observed: 1) hypoinsulinemia, 2) insulinotropic effects of both GIP and GLP-1, 3) <a>additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP1, respectively, </a>and 4) increased fasting and arginine-induced glucagon levels compared to non-diabetic controls. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A-diabetes via potentiation of glucose-stimulated insulin secretion.

scholarly journals Proteomic screen defines the hepatocyte nuclear factor 1α-binding partners and identifies HMGB1 as a new cofactor of HNF1α

2007 ◽  
Vol 36 (4) ◽  
pp. 1209-1219 ◽  
Author(s):  
Miao Yu ◽  
Jian Wang ◽  
Wei Li ◽  
Yan Zhi Yuan ◽  
Chang Yan Li ◽  
...  
Keyword(s):  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Proteomic Screen ◽  
Binding Partners ◽  
Hepatocyte Nuclear Factor 1Α

scholarly journals Hepatocyte Nuclear Factor-1α, GATA-4, and Caudal Related Homeodomain Protein Cdx2 Interact Functionally to Modulate Intestinal Gene Transcription

2002 ◽  
Vol 277 (35) ◽  
pp. 31909-31917 ◽  
Author(s):  
François Boudreau ◽  
Edmond H. H. M. Rings ◽  
Herbert M. van Wering ◽  
Richard K. Kim ◽  
Gary P. Swain ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Homeodomain Protein ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 1Α

Loss of hepatocyte nuclear factor 1α function in human hepatocellular adenomas leads to aberrant activation of signaling pathways involved in tumorigenesis

Hepatology ◽  
2009 ◽  
Vol 51 (2) ◽  
pp. 557-566 ◽  
Author(s):  
Laura Pelletier ◽  
Sandra Rebouissou ◽  
Alain Paris ◽  
Estelle Rathahao-Paris ◽  
Elisabeth Perdu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Hepatocellular Adenomas

scholarly journals Serum magnesium, hepatocyte nuclear factor 1β genotype and post-transplant diabetes mellitus: a prospective study

2019 ◽  
Author(s):  
Anna C van der Burgh ◽  
Arthur Moes ◽  
Brenda C T Kieboom ◽  
Teun van Gelder ◽  
Robert Zietse ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factor ◽  
Insulin Secretion ◽  
Prospective Study ◽  
Serum Magnesium ◽  
First Year ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Lower Serum ◽  
A Prospective Study

Abstract Background Retrospective studies suggest that tacrolimus-induced hypomagnesaemia is a risk factor for post-transplant diabetes mellitus (PTDM), but prospective studies are lacking. Methods This was a prospective study with measurements of serum magnesium and tacrolimus at pre-specified time points in the first year after living donor kidney transplantation (KT). The role of single nucleotide polymorphisms (SNPs) in hepatocyte nuclear factor 1β (HNF1β) was also explored because HNF1β regulates insulin secretion and renal magnesium handling. Repeated measurement and regression analyses were used to analyse associations with PTDM. Results In our cohort, 29 out of 167 kidney transplant recipients developed PTDM after 1 year (17%). Higher tacrolimus concentrations were significantly associated with lower serum magnesium and increased risk of hypomagnesaemia. Patients who developed PTDM had a significantly lower serum magnesium trajectory than patients who did not develop PTDM. In multivariate analysis, lower serum magnesium, age and body mass index were independent risk factors for PTDM. In recipients, the HNF1β SNP rs752010 G > A significantly increased the risk of PTDM [odds ratio (OR) = 2.56, 95% confidence interval (CI) 1.05–6.23] but not of hypomagnesaemia. This association lost significance after correction for age and sex (OR = 2.24, 95% CI 0.90–5.57). No association between HNF1β SNPs and PTDM was found in corresponding donors. Conclusions A lower serum magnesium in the first year after KT is an independent risk factor for PTDM. The HNF1β SNP rs752010 G > A may add to this risk through an effect on insulin secretion rather than hypomagnesaemia, but its role requires further confirmation.

scholarly journals Characterization of Human Pterin-4a-carbinolamine Dehydratase/Dimerization Cofactor of Hepatocyte Nuclear Factor-1α, and of the Cys81-mutant Involved in Hyperphenylalanincemia

Pteridines ◽  
1995 ◽  
Vol 6 (3) ◽  
pp. 123-125 ◽  
Author(s):  
Sandra Köster ◽  
Beat Thöny ◽  
Peter Macheroux ◽  
Hans-Christoph Curtius ◽  
Claus W. Heizmann ◽  
...  
Keyword(s):  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 1Α
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