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Loss of glucose sensing with vagal neurocircuits contributes to glycemic dysregulation and gastrointestinal dysfunction in a mouse model of Type 2 diabetes
Summary Data Summary
Applicant Browning, Kirsteen
E-Mail Address knb13@psu.edu
Project Title Loss of glucose sensing with vagal neurocircuits contributes to glycemic
dysregulation and gastrointestinal dysfunction in a mouse model of Type 2
diabetes
CBU ID 14GHSU1378
External SubContract ID 25732-53
Diabetic Complication Gastro-Intestinal (GI)
Funding Program Group Pilot & Feasibility [PF2014]
Abstract Diabetic gastroparesis, (delayed gastric emptying associated with other upper
gastrointestinal (GI) symptoms such as early satiety, fullness, abdominal pain,
nausea and bloating) is experienced by up to 65% of patients with Type 2
diabetes. Despite the annual US economic cost of diabetic gastroparesis
(estimated at approximately $3.5 billion) and the considerable impact upon the
quality of life of patients, the pathophysiology of diabetic gastroparesis
remains to be elucidated fully. Although the GI tract possesses intrinsic neural
plexuses that allow a significant degree or autonomy over GI functions, the
parasympathetic nervous system, via the vagus nerve, exerts a finely-tuned and
complex influence over GI functions including motility, tone and emptying.
Studies in both humans and animal models have demonstrated that vagal control of
the stomach and upper GI tract is modulated by physiological fluctuations in
glycemic levels and is compromised by hyperglycemia and long-standing diabetes;
the mechanism by which this maladaptation occurs has not been investigated. Our
preliminary evidence has led to the novel central hypothesis that loss of
glucose sensing within vagal neurocircuits precedes, and may even contribute to,
the development of glycemic dysregulation and GI dysfunction.
In the present study, we will use a congenic strain of mice, the NONcNZO10/LtJ
mouse that was developed to mimic human obesity-induced Type 2 diabetes and
metabolic syndrome. This mouse provides an excellent (though to date unstudied)
translational model in which a multi-system disease such as diabetes can be
investigated on complex autonomic outcomes such as gastrointestinal functions.
To investigate the pathophysiology of diabetic gastroparesis, we will use a
variety of techniques to correlate the time-course and onset of disrupted vagal
neural signaling with dysregulated gastric functions. We anticipated that the
results from the present proposal will provide information regarding the
temporal nature of diabetes-induced dysregulation within vagal neurocircuits
controlling GI functions as well as the insights into the mechanism behind these
alterations
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 19557
Supply Total Costs 45802
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 65359
Indirect Costs Proposed 34640
Total Costs Proposed 99999
Total Costs Approved 99999
Start Date 10/1/2014
End Date 9/30/2015
IFO Name Falvo, Vincent
IFO E-Mail Address vfalvo@hmc.psu.edu
IACUC/IRB No. 999999
IACUC/IRB Institution Pennsylvania State University-Penn State College of Medicine
Entity ID No. 1246000376
Report Request Date 10/30/2015
T1D NO
TypeCount
Invoices 22
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine9/29/2016$1,856.89$984.16$2,841.05-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine9/22/2016$9,459.40$5,013.47$14,472.87-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine9/11/2015$7,166.03-$7,166.03-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine8/9/2016$8,457.42$4,482.43$12,939.85-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine8/11/2015$2,141.51-$2,141.51-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine7/24/2015$2,052.71-$2,052.71-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine7/18/2016$1,398.30$741.10$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine6/17/2016$1,398.30$741.10$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine6/10/2015$2,052.71-$2,052.71-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine5/6/2015$2,052.71-$2,052.71-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine5/25/2016$1,398.30$741.10$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine4/6/2015$2,044.21-$2,044.21-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine4/22/2016$1,398.30$741.10$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine3/6/2015$2,196.28-$2,196.28-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine3/15/2016$1,398.30$741.10$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine2/19/2016$4,629.72$2,453.75$7,083.47-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine2/13/2015$420.32-$420.32-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine12/8/2015$2,139.40-$2,139.40-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine11/12/2015$3,625.21-$3,625.21-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine10/8/2015$2,141.51-$2,141.51-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine1/9/2017$12,954.50$6,865.88$19,820.38-View PDF
  View  14GHSU137825732-53Pennsylvania State University-Penn State College of Medicine1/13/2016$4,111.78-$4,111.78-View PDF
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