ArticleDiabetologia2014
High heritability and genetic correlation of intravenous glucose- and tolbutamide-induced insulin secretion among non-diabetic family members of type 2 diabetic patients.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Pooled it
- Berberine is an insulin secretagogue targeting the KCNH6 potassium channel.Nature communications · 2021Trial
- Genetic Underpinnings of Fasting and Oral Glucose-stimulated Based Insulin Sensitivity Indices.The Journal of clinical endocrinology and metabolism · 2024Article
- Article
- Genetic insights into fetal growth and measures of glycaemic regulation and adiposity in adulthood: a family-based study.BMC medical genetics · 2018Article
- A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes: The Hortega study.Redox biology · 2017Article
- Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery.Nature reviews. Endocrinology · 2016Review
- The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus.Journal of gastroenterology · 2016Article
- Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology.PloS one · 2016Article
- Article
- A low disposition index in adolescent offspring of mothers with gestational diabetes: a risk marker for the development of impaired glucose tolerance in youth.Diabetologia · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe aim of this study was to estimate the heritability of quantitative measures of glucose regulation obtained from a tolbutamide-modified frequently sampled IVGTT (t-FSIGT) and to correlate the heritability of the glucose-stimulated beta cell response to the tolbutamide-induced beta cell response. In addition, single nucleotide polymorphisms (SNPs) having an exclusive effect on either glucose- or tolbutamide-stimulated insulin release were identified.
methodsTwo hundred and eighty-four non-diabetic family members of patients with type 2 diabetes underwent a t-FSIGT with intravenous injection of glucose at t = 0 min and tolbutamide at t = 20 min. Measurements of plasma glucose, serum insulin and serum C-peptide were taken at 33 time points from fasting to 180 min. Insulin secretion rate, acute insulin response (AIR), disposition index (DI) after glucose and disposition index after tolbutamide (DIT), insulin sensitivity (SI), glucose effectiveness (SG) and beta cell responsiveness to glucose were calculated. A polygenic variance component model was used to estimate heritability, genetic correlations and associations.
resultsWe found high heritabilities for acute insulin secretion subsequent to glucose stimulation (AIRglucose h (2) ± SE: 0.88 ± 0.14), but these were slightly lower after tolbutamide (AIRtolbutamide h (2) ± SE: 0.69 ± 0.14). We also estimated the heritabilities for SI (h (2) ± SE: 0.26 ± 0.12), SG (h (2) ± SE: 0.47 ± 0.13), DI (h (2) ± SE: 0.56 ± 0.14), DIT (h (2) ± SE: 0.49 ± 0.14) and beta cell responsiveness to glucose (h (2) ± SE: 0.66 ± 0.12). Additionally, strong genetic correlations were found between measures of beta cell response after glucose and tolbutamide stimulation, with correlation coefficients ranging from 0.77 to 0.88. Furthermore, we identified five SNPs with an exclusive effect on either glucose-stimulated (rs5215, rs1111875, rs11920090) or tolbutamide-stimulated (rs10946398, rs864745) insulin secretion. CONCLUSIONS/
interpretationOur data demonstrate that both glucose- and tolbutamide-induced insulin secretions are highly heritable traits, which are largely under the control of the same genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.