Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus

Shariq I. Sherwani, Carolyn Aldana, Saif Usmani, Christopher Adin, Sainath Kotha, Mahmood Khan, Timothy Eubank, Philipp E. Scherer, Narasimham Parinandi, Ulysses J. Magalang

Research output: Contribution to journalArticle

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Abstract

Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes. Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist. Measurements and Results: During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. Conclusions: Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects.

Original languageEnglish (US)
Pages (from-to)1849-1858
Number of pages10
JournalSleep
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2013

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Diabetes Mellitus
Islets of Langerhans
Insulin
Adrenergic Agonists
Fatty Acids
Glucose Tolerance Test
Nonesterified Fatty Acids
Rodentia
Hypoxia
Stearic Acids
Monounsaturated Fatty Acids
Oximetry
Palmitic Acid
Electron Spin Resonance Spectroscopy
Caspase 3
Type 2 Diabetes Mellitus
Pancreas
Cell Survival
Air
Apoptosis

Keywords

  • β-cell function
  • Diabetes mellitus
  • Fatty acids
  • Intermittent hypoxia

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

Cite this

Sherwani, S. I., Aldana, C., Usmani, S., Adin, C., Kotha, S., Khan, M., ... Magalang, U. J. (2013). Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus. Sleep, 36(12), 1849-1858. https://doi.org/10.5665/sleep.3214

Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus. / Sherwani, Shariq I.; Aldana, Carolyn; Usmani, Saif; Adin, Christopher; Kotha, Sainath; Khan, Mahmood; Eubank, Timothy; Scherer, Philipp E.; Parinandi, Narasimham; Magalang, Ulysses J.

In: Sleep, Vol. 36, No. 12, 01.12.2013, p. 1849-1858.

Research output: Contribution to journalArticle

Sherwani, SI, Aldana, C, Usmani, S, Adin, C, Kotha, S, Khan, M, Eubank, T, Scherer, PE, Parinandi, N & Magalang, UJ 2013, 'Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus', Sleep, vol. 36, no. 12, pp. 1849-1858. https://doi.org/10.5665/sleep.3214
Sherwani SI, Aldana C, Usmani S, Adin C, Kotha S, Khan M et al. Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus. Sleep. 2013 Dec 1;36(12):1849-1858. https://doi.org/10.5665/sleep.3214
Sherwani, Shariq I. ; Aldana, Carolyn ; Usmani, Saif ; Adin, Christopher ; Kotha, Sainath ; Khan, Mahmood ; Eubank, Timothy ; Scherer, Philipp E. ; Parinandi, Narasimham ; Magalang, Ulysses J. / Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus. In: Sleep. 2013 ; Vol. 36, No. 12. pp. 1849-1858.
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abstract = "Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes. Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist. Measurements and Results: During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. Conclusions: Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects.",
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AU - Adin, Christopher

AU - Kotha, Sainath

AU - Khan, Mahmood

AU - Eubank, Timothy

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AU - Parinandi, Narasimham

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N2 - Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes. Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist. Measurements and Results: During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. Conclusions: Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects.

AB - Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes. Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist. Measurements and Results: During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. Conclusions: Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects.

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KW - Diabetes mellitus

KW - Fatty acids

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