Dataset Information

The Impact of Dopamine on Insulin Secretion in Healthy Controls.

ABSTRACT:

Objective

Dopamine is very commonly used in the critical care setting and impacts glucose homeostasis. In some studies, it is noted to increase insulin resistance or decrease insulin secretion. The role of insulin secretion in response to dopamine is incompletely understood.

Methods

Eight individuals underwent a hyperglycemic clamp with a dopamine infusion, and eight controls underwent hyperglycemic clamp alone. Insulin, C-peptide, glucagon, cortisol, and norepinephrine (NE) concentrations were measured at various time points. An index of insulin sensitivity (M/I) was calculated. Statistical comparison between the control and treatment arm was done using repeated measures ANOVA. The data is expressed as mean ± standard deviation. Paired t-test was used to compare pre- and post-dopamine infusion time points in the study individuals only. Data was considered to be statistically significant at P < 0.05.

Results

On assessing the treatment group before and during dopamine infusion, insulin and C-peptide concentrations were higher at the time of the infusion (P = 0.02 and P = 0.003, respectively). The index of insulin sensitivity was not statistically different. There was a significant decrease in insulin (P = 0.002), C-peptide (P = 0.005), and NE (P < 0.0001) concentrations in the treatment group, compared to the controls. Glucagon concentration was higher in the treatment group (P = 0.02).

Conclusion

In this study, dopamine infusion did not adversely impact insulin secretion.

SUBMITTER: Underland LJ

PROVIDER: S-EPMC5930523 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

The Impact of Dopamine on Insulin Secretion in Healthy Controls.

Underland Lisa J LJ Mark Erika R ER Katikaneni Ranjitha R Heptulla Rubina R

Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine 20180401 4

<h4>Objective</h4>Dopamine is very commonly used in the critical care setting and impacts glucose homeostasis. In some studies, it is noted to increase insulin resistance or decrease insulin secretion. The role of insulin secretion in response to dopamine is incompletely understood.<h4>Methods</h4>Eight individuals underwent a hyperglycemic clamp with a dopamine infusion, and eight controls underwent hyperglycemic clamp alone. Insulin, C-peptide, glucagon, cortisol, and norepinephrine (NE) conce ...[more]

PMID: 29743758

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Project description:Pancreatic beta cell function is an important component of glucose homeostasis. Here, we investigated the function of PIMT (PRIP-interacting protein with methyl transferase domain), a transcriptional co-activator binding protein, in the pancreatic beta cells. We observed that the protein levels of PIMT, along with key beta cell markers such as PDX1 (pancreatic and duodenal homeobox 1) and MafA (MAF bZIP transcription factor A), were reduced in the beta cells exposed to hyperglycemic and hyperlipidemic conditions. Consistently, PIMT levels were reduced in the pancreatic islets isolated from high fat diet (HFD)-fed mice. The RNA sequencing analysis of PIMT knockdown beta cells identified that the expression of key genes involved in insulin secretory pathway, Ins1 (insulin 1), Ins2 (insulin 2), Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Kcnn1 (potassium calcium-activated channel subfamily N member 1), Rab3a (member RAS oncogene family), Gnas (GNAS complex locus), Syt13 (synaptotagmin 13), Pax6 (paired box 6), Klf11 (Kruppel-Like Factor 11), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1) was attenuated due to PIMT depletion. PIMT ablation in the pancreatic beta cells and in the rat pancreatic islets led to decreased protein levels of PDX1 and MafA, resulting in the reduction in glucose-stimulated insulin secretion (GSIS). The results from the immunoprecipitation and ChIP experiments revealed the interaction of PIMT with PDX1 and MafA, and its recruitment to the insulin promoter, respectively. Importantly, PIMT ablation in beta cells resulted in the nuclear translocation of insulin. Surprisingly, forced expression of PIMT in beta cells abrogated GSIS, while Ins1 and Ins2 transcript levels were subtly enhanced. On the other hand, the expression of genes, PRIP/Asc2/Ncoa6 (nuclear receptor coactivator 6), Pax6, Kcnj11, Syt13, Stxbp1 (syntaxin binding protein 1), and Snap25 (synaptosome associated protein 25) associated with insulin secretion, was significantly reduced, providing an explanation for the decreased GSIS upon PIMT overexpression. Our findings highlight the importance of PIMT in the regulation of insulin synthesis and secretion in beta cells.

Dataset Information

The Impact of Dopamine on Insulin Secretion in Healthy Controls.

Objective

Methods

Results

Conclusion

Publications

The Impact of Dopamine on Insulin Secretion in Healthy Controls.

Similar Datasets

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