Genetic influences on the insulin response of the beta cell to different secretagogues

Abstract

Aims/hypothesis The aim of the present study was to estimate the heritability of the beta cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine. Methods This was a twin-family study that included 54 families from the Netherlands Twin Register. The participants were healthy twin pairs and their siblings of the same sex, aged 20 to 50 years. Insulin response of the beta cell was assessed by a modified hyperglycaemic clamp with additional GLP-1 and arginine. Insulin sensitivity index (ISI) was assessed by the euglycaemic-hyperinsulinaemic clamp. Multivariate structural equation modelling was used to obtain heritabilities and the genetic factors underlying individual differences in BMI, ISI and secretory responses of the beta cell. Results The heritability of insulin levels in response to glucose was 52% and 77% for the first and second phase, respectively, 53% in response to glucose+GLP-1 and 80% in response to an additional arginine bolus. Insulin responses to the administration of glucose, glucose+GLP-1 and glucose + GLP-1 + arginine were highly correlated (0.62<r<0.79). Heritability of BMI and ISI was 74% and 60% respectively. The genetic factors that influenced BMI and ISI explained about half of the heritability of insulin levels in response to the three secretagogues. The other half was due to genetic factors specific to the beta cell. Conclusions/interpretation In healthy adults, genetic factors explain most of the individual differences in the secretory capacity of the beta cell. These genetic influences are partly independent from the genes that influence BMI and ISI.

Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control

“…The study protocol was approved by the Medical Ethics Committee of the VU University Medical Center (VUmc) and all participants gave informed consent. Only healthy participants were included, for further inclusion and exclusion criteria see Simonis-Bik et al [21]. Overall, 130 participants (100 twins and 30 siblings) participated in both a euglycaemichyperinsulinaemic clamp and a modified hyperglycaemic clamp.…”

“…The euglycaemic clamp was performed as in SimonisBik et al [21] and the modified hyperglycaemic clamp was performed as described previously in Simonis-Bik et al and Fritsche et al [21,22] Fig. 1 as the small black squares just above the timeline).…”

Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of glucocorticoids in men with the metabolic syndrome? A randomized controlled trial

“…However, previous studies did not show an effect of GCs on (active) incretin levels (6, 33, 34). We deliberately chose to include white men, as ethnicity and gender may be effect modifiers of several treatment-related study variables (40). However, this approach precludes generalization of the results.…”

Fasting and oral glucose-stimulated levels of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are highly familial traits

“…Incretins are important glucose-dependent insulinotropic hormones released from the intestine after meal ingestion. While an absent or grossly impaired incretin effect characterises type 2 diabetes [21][22][23], the degree to which genetics regulate measures of the incretin system has been previously investigated in only one study, showing that genes accounted for 53% of the beta cell response to exogenous glucagon-like peptide-1 (GLP-1) among 100 twins and 25 siblings (hyperglycaemic clamp) [24].…”