Monogenic diabetes in children and young adults: Challenges for researcher, clinician and patient

Slingerland, Annabelle S.

doi:10.1007/s11154-006-9014-0

Cited by 41 publications

(34 citation statements)

References 77 publications

(91 reference statements)

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“…Extrapolation of the diabetic animal models predicts that overactive β-cell K ATP may underlie impaired insulin release and NDM in humans. NDM is a rare disorder with an incidence 1:300,000 live births that is diagnosed within the first 6 months of life and, until recently, typically required insulin therapy [96,118]. In the milder transient form (TNDM), hyperglycemia usually resolves within 18 months of life, but there is an increased risk for relapse during pubescence, whereas, the permanent form (PNDM) requires lifelong glycemic control.…”

Section: Role Of K Atp In Insulin Secretion From the Pancreatic β-Cellmentioning

confidence: 99%

KATP channelopathies in the pancreas

Remedi

Koster

2009

Pflugers Arch - Eur J Physiol

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Adenosine-triphosphate-sensitive potassium channels (KATP) are regulated by adenosine nucleotides, and, thereby, couple cellular metabolism with electrical activity in multiple tissues including the pancreatic beta-cell. The critical involvement of KATP in insulin secretion is confirmed by the demonstration that inactivating and activating mutations in KATP underlie persistent hyperinsulinemia and neonatal diabetes mellitus, respectively, in both animal models and humans. In addition, a common variant in KATP represents a risk factor in the etiology of type 2 diabetes. This review focuses on the mechanistic basis by which KATP mutations underlie insulin secretory disorders and the implications of these findings for successful clinical intervention.

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Section: Role Of K Atp In Insulin Secretion From the Pancreatic β-Cellmentioning

confidence: 99%

KATP channelopathies in the pancreas

Remedi

Koster

2009

Pflugers Arch - Eur J Physiol

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“…hypertension and diabetes mellitus [7], [8]. However, it is important to note that the polygenic forms of these diseases including hypercalciuric nephrolithiasis are more common, whereas the familial monogenic forms are rare [9], and that the study of both forms has yielded important and novel insights of homeostatic mechanisms and their roles in disease processes. This is well illustrated by studies of the different forms of hypercalciuric nephrolithiasis.…”

Section: Introductionmentioning

confidence: 99%

Autosomal Dominant Hypercalciuria in a Mouse Model Due to a Mutation of the Epithelial Calcium Channel, TRPV5

et al. 2013

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Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5) and 6 (Trpv6) genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P). Compared to wild-type littermates, heterozygous (Trpv5 682P/+) and homozygous (Trpv5 682P/682P) mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5 682P/682P mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D3 concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5 682P/+ and Trpv5 682P/682P mice consistent with a trafficking defect. In addition, Trpv5682P/682P mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D28K, consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings indicate that the TRPV5 S682P mutant is functionally significant and study of HCALC1, a novel model for autosomal dominant hypercalciuria, may help further our understanding of renal calcium reabsorption and hypercalciuria.

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“…MODY 3 diabetes is associated with a progressive decrease in insulin secretion. Two‐thirds of patients need treatment with oral hypoglycemic drugs (OHD) or insulin [8–10]. MODY5 related mutations (also called renal cysts and diabetes, RCAD) generate diabetes in only 50% of patients;[11] with most of them necessitating insulin [12].…”

Section: Introductionmentioning

confidence: 99%

Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience

Poitou¹,

François²,

Bellanné‐Chantelot³

et al. 2012

Transplant International

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The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.

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Monogenic diabetes in children and young adults: Challenges for researcher, clinician and patient

Cited by 41 publications

References 77 publications

KATP channelopathies in the pancreas

KATP channelopathies in the pancreas

Autosomal Dominant Hypercalciuria in a Mouse Model Due to a Mutation of the Epithelial Calcium Channel, TRPV5

Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience

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