SEPSIS INDUCED INSULIN RESISTANCE IN DIABETES

Project: Research project

Description

It appears that patients with diabetes mellitus are predisposed to
gram-negative infections. Anecdotal evidence suggests that septicemia in
these individuals is associated with an increased insulin requirement;
however, systematic studies concerning changes in insulin sensitivity in
the diabetic during infection are lacking. The long-term goal of this
research is to define mechanisms responsible for the increased insulin
resistance following bacterial infection in diabetic patients, compare
these to changes seen in nondiabetic individuals during sepsis, and
ultimately to identify the consequences of these changes on the recovery of
both patient populations. Two working hypotheses will be considered: (1)
gram-negative infection further impairs both glucose- and insulin- mediated
regulation of glucose production and utilization in chronic diabetes, and
(2) the sepsis-induced increase in circulating concentrations of
counterregulatory hormones are responsible for the increased insulin
resistance in sepsis. These experiments will utilize chronically
catheterized conscious nondiabetic and diabetic (streptozotocin) rats.
Sepsis will be induced in both groups by subcutaneous injection of live E.
coli. Hypothesis 1 will be addressed by specific aims which determine
glucose kinetics, hepatic and muscle glycogen reserves and the activity of
rate-controlling enzymes of glycogen metabolism in the basal state.
Second, insulin resistance will be quantitated in vivo by determining the
rate of glucose disposal using euglycemic and hyperglycemic insulin
clamps. These studies will also provide information on the balance between
glycogen synthesis and glucose output by the liver by determining the fate
of gluconeogenically derived glucose-6-phosphate. Third, in vivo insulin
dose-response curves for selected individual tissues will be determined
using 3H-2-deoxyglucose. Hypothesis 2 will be tested by using glycemic
clamp techniques and selectively lowering the plasma concentration (e.g.,
glucagon, corticosterone and growth hormone) or blocking the action (e.g.,
catecholamines) of one of the counterregulatory hormones. These studies
will provide definitive information on whole body and tissue insulin
sensitivity in sepsis and diabetes and the interaction of these two
conditions. It will also aid in understanding the factors which make
diabetics more susceptible to gram-negative infections.
StatusFinished
Effective start/end date4/1/875/31/17

Funding

  • National Institutes of Health: $330,879.00
  • National Institutes of Health: $100,230.00
  • National Institutes of Health: $304,583.00
  • National Institutes of Health: $329,563.00
  • National Institutes of Health: $272,800.00
  • National Institutes of Health: $378,076.00
  • National Institutes of Health
  • National Institutes of Health: $272,960.00
  • National Institutes of Health
  • National Institutes of Health: $311,940.00
  • National Institutes of Health: $326,211.00
  • National Institutes of Health: $378,076.00
  • National Institutes of Health: $166,577.00
  • National Institutes of Health: $272,882.00
  • National Institutes of Health
  • National Institutes of Health: $378,076.00
  • National Institutes of Health
  • National Institutes of Health: $237,574.00
  • National Institutes of Health: $332,772.00
  • National Institutes of Health
  • National Institutes of Health: $364,842.00
  • National Institutes of Health: $311,967.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $61,560.00
  • National Institutes of Health
  • National Institutes of Health: $185,252.00
  • National Institutes of Health: $272,715.00
  • National Institutes of Health
  • National Institutes of Health: $295,722.00
  • National Institutes of Health

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Sepsis
Muscle Proteins
Cytokines
Infection
Somatomedins
Insulin Resistance
Muscles
Growth Hormone
Insulin
Glucose
Skeletal Muscle
Insulin-Like Growth Factor I
Myostatin
Muscular Diseases
Food
Leucine
Glucocorticoids
Wounds and Injuries
Phosphotransferases
Research