Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Adrenergic desensitization in left ventricle from streptozotocin diabetic swine.

Publication ,  Journal Article
Roth, DA; White, CD; Hamilton, CD; Hall, JL; Stanley, WC
Published in: J Mol Cell Cardiol
October 1995

Patients with diabetes mellitus that exhibit cardiac pump failure display compromised stroke volume, ejection fraction, and slower rates of rise and fall of left ventricular (LV) dP/dt in the absence of ischemic injury. We hypothesized that diabetic cardiomyopathy may involve decrements in adrenergic sensitivity, with specific molecular alterations in the beta-adrenergic receptor (beta AR)- G protein- adenylyl cyclase (AC) signal transduction system. We assessed the effects of 3 months of streptozotocin-induced diabetes (125 mg/kg i.v.; DIAB, n = 10) on myocardial signal transduction in mini-pigs. DIAB were hyperglycemic compared to controls (CON, n = 10; 20.92 +/- 2.64 v 5.24 +/- 0.35 mM glucose), and had lower fasting insulin levels (6.46 +/- 0.97 v 13.68 +/- 3.91 microU/ml). Transmural LV free wall homogenates from DIAB exhibited similar beta AR density as CON, but decreased cAMP production (pmol cAMP/mg prot.min) using these pharmacological stimulators: 10 microM Isoproterenol plus 100 microM GTP (74 +/- 5 v 97 +/- 11); 100 microM Gpp(NH)p (116 +/- 7 v 161 +/- 17); 10 mM fluoride ion (266 +/- 16 v 324 +/- 25). No differences between DIAB and CON were observed when stimulated by 100 microM forskolin (440 +/- 20 v 429 +/- 33), suggesting no alterations in the catalytic subunit of AC. In DIAB, quantitative immunoblotting indicated slightly depressed levels of Gs (552 +/- 44 v 630 +/- 59 pmol/g ww; NS), but a significant redistribution of alpha s from the sarcolemma to the cytosol (32.7 +/- 0.82% v 25.9 +/- 1.7%). Significantly elevated levels of cardiac Gi were seen in DIAB homogenates compared to CON ventricles (2326 +/- 145 v 1522 +/- 181 pmol/g ww), with no alpha i subunit redistribution. We conclude that despite maintained beta AR density, receptor-dependent and G protein-dependent stimulation of AC is depressed so that streptozotocin-induced diabetic LV is affected by increased cardiac Gi, redistribution of Gs alpha to the cytosol, and an increase in the Gi/Gs ratio. These results help explain depressed catecholamine responsiveness and cardiac performance exhibited by diabetic patients.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

October 1995

Volume

27

Issue

10

Start / End Page

2315 / 2325

Location

England

Related Subject Headings

  • Swine, Miniature
  • Swine
  • Streptozocin
  • Signal Transduction
  • Sarcolemma
  • Receptors, Adrenergic, beta
  • Isoproterenol
  • Insulin
  • Heart Ventricles
  • Guanosine Triphosphate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Roth, D. A., White, C. D., Hamilton, C. D., Hall, J. L., & Stanley, W. C. (1995). Adrenergic desensitization in left ventricle from streptozotocin diabetic swine. J Mol Cell Cardiol, 27(10), 2315–2325. https://doi.org/10.1016/s0022-2828(95)91875-2
Roth, D. A., C. D. White, C. D. Hamilton, J. L. Hall, and W. C. Stanley. “Adrenergic desensitization in left ventricle from streptozotocin diabetic swine.J Mol Cell Cardiol 27, no. 10 (October 1995): 2315–25. https://doi.org/10.1016/s0022-2828(95)91875-2.
Roth DA, White CD, Hamilton CD, Hall JL, Stanley WC. Adrenergic desensitization in left ventricle from streptozotocin diabetic swine. J Mol Cell Cardiol. 1995 Oct;27(10):2315–25.
Roth, D. A., et al. “Adrenergic desensitization in left ventricle from streptozotocin diabetic swine.J Mol Cell Cardiol, vol. 27, no. 10, Oct. 1995, pp. 2315–25. Pubmed, doi:10.1016/s0022-2828(95)91875-2.
Roth DA, White CD, Hamilton CD, Hall JL, Stanley WC. Adrenergic desensitization in left ventricle from streptozotocin diabetic swine. J Mol Cell Cardiol. 1995 Oct;27(10):2315–2325.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

October 1995

Volume

27

Issue

10

Start / End Page

2315 / 2325

Location

England

Related Subject Headings

  • Swine, Miniature
  • Swine
  • Streptozocin
  • Signal Transduction
  • Sarcolemma
  • Receptors, Adrenergic, beta
  • Isoproterenol
  • Insulin
  • Heart Ventricles
  • Guanosine Triphosphate