Recurrent Moderate Hypoglycemia (RH) Enhances Cardiac Mitochondrial Respiration in Diabetic Rats

Sathya Velmurugan; Simon Fisher; Velmurugan Gopal Viswanathan; Patrick Sullivan

doi:10.2337/db25-50-OR

Abstract

Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function.

Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4.

Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA).

Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.

Original language	American English
DOIs	https://doi.org/10.2337/db25-50-OR
State	Published - Jun 20 2025
Event	American Diabetes Association: Scientific Sessions - Florida, Orlando, United States Duration: Jun 1 2018 → …

Conference

Conference	American Diabetes Association
Country/Territory	United States
City	Orlando
Period	6/1/18 → …

Funding

Advancing Research Collaborations Award 2024 from Barnstable Brown Diabetes Center and Diabetes and Obesity Research Priority Area, University of Kentucky

Funders
Barnstable Brown Diabetes Center
Diabetes and Obesity Research Priority Initiative

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.2337/db25-50-OR

1 Finished

Preventing severe hypoglycemia-induced cardiac arrhythmia
Velmurugan, S. (PI)
University of Kentucky Diabetes and Obesity Research Priority Area
5/1/24 → 4/30/25
Project: Research project

ChemiDoc Imaging System Bio-Rad
Stowe, A. (Manager), Chen, M. (Operator), Hubbard, W. (Operator), Gipson-Reichardt, C. (Operator), Sullivan, P. (Operator), Roberts, J. (Operator), Trout, A. (Operator), Whiteheart, S. (Operator) & Wood, J. (Operator)
Neuroscience Research Priority Area
Equipment/facility: Equipment

Poster Presentation: First Prize – Faculty Category
Velmurugan, S. (Recipient), May 22 2025
Prize

Cite this

@conference{32670bc0e4d1455ab9fafe622f256a0d,

title = "Recurrent Moderate Hypoglycemia (RH) Enhances Cardiac Mitochondrial Respiration in Diabetic Rats",

abstract = "Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function. Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4. Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA). Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.",

author = "Sathya Velmurugan and Simon Fisher and \{Gopal Viswanathan\}, Velmurugan and Patrick Sullivan",

year = "2025",

month = jun,

day = "20",

doi = "10.2337/db25-50-OR",

language = "American English",

note = "American Diabetes Association : Scientific Sessions ; Conference date: 01-06-2018",

}

TY - CONF

T1 - Recurrent Moderate Hypoglycemia (RH) Enhances Cardiac Mitochondrial Respiration in Diabetic Rats

AU - Velmurugan, Sathya

AU - Fisher, Simon

AU - Gopal Viswanathan, Velmurugan

AU - Sullivan, Patrick

PY - 2025/6/20

Y1 - 2025/6/20

N2 - Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function. Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4. Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA). Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.

AB - Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function. Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4. Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA). Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.

U2 - 10.2337/db25-50-OR

DO - 10.2337/db25-50-OR

M3 - Abstract

T2 - American Diabetes Association

Y2 - 1 June 2018

ER -

Recurrent Moderate Hypoglycemia (RH) Enhances Cardiac Mitochondrial Respiration in Diabetic Rats

Abstract

Conference

Funding

UN SDGs

Access to Document

Fingerprint

Projects

Preventing severe hypoglycemia-induced cardiac arrhythmia

Equipment

ChemiDoc Imaging System Bio-Rad

Prizes

Poster Presentation: First Prize – Faculty Category

Cite this