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Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion

Salunkhe, Vishal A. LU ; Mollet, Ines LU ; Ofori, Jones K. LU ; Malm, Helena A. LU ; Esguerra, Jonathan L S LU ; Reinbothe, Thomas LU ; Stenkula, Karin G. LU ; Wendt, Anna LU ; Eliasson, Lena LU and Vikman, Jenny LU (2016) In EBioMedicine 10. p.185-194
Abstract

Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca2+ signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and... (More)

Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca2+ signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipose tissue, Beta cell, Ca measurements, Glucose homeostasis, Glucose uptake, Insulin secretion, Islet, Muscle, OGTT, Statin, Transmission electron microscopy
in
EBioMedicine
volume
10
pages
185 - 194
publisher
Elsevier
external identifiers
  • scopus:85003023607
  • wos:000386877700029
ISSN
2352-3964
DOI
10.1016/j.ebiom.2016.07.007
language
English
LU publication?
yes
id
1d667561-d4a8-4a28-885a-02d01a9ce775
date added to LUP
2016-12-30 11:00:46
date last changed
2017-09-18 11:34:44
@article{1d667561-d4a8-4a28-885a-02d01a9ce775,
  abstract     = {<p>Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca<sup>2+</sup> signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.</p>},
  author       = {Salunkhe, Vishal A. and Mollet, Ines and Ofori, Jones K. and Malm, Helena A. and Esguerra, Jonathan L S and Reinbothe, Thomas and Stenkula, Karin G. and Wendt, Anna and Eliasson, Lena and Vikman, Jenny},
  issn         = {2352-3964},
  keyword      = {Adipose tissue,Beta cell,Ca measurements,Glucose homeostasis,Glucose uptake,Insulin secretion,Islet,Muscle,OGTT,Statin,Transmission electron microscopy},
  language     = {eng},
  pages        = {185--194},
  publisher    = {Elsevier},
  series       = {EBioMedicine},
  title        = {Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion},
  url          = {http://dx.doi.org/10.1016/j.ebiom.2016.07.007},
  volume       = {10},
  year         = {2016},
}