LPS-dependent suppression of social exploration is augmented in type 1 diabetic mice.
We have previously shown that type 2 diabetes (T2D) in the mouse is associated with increased responsivity to innate immune challenge. Here we demonstrate that in a mouse model of type 1 diabetes (T1D) LPS-dependent suppression of social exploration (SE) is augmented and dependent on hyperglycemia. T1D was induced in mice with intraperitoneal (i.p.) streptozotocin (STZ). After 4d, STZ treated mice had blood glucose levels of 417+/-34mg/dl compared to 160+/-11mg/dl in non-STZ treated mice. When these diabetic mice were challenged with i.p. lipopolysaccharide (LPS), LPS-induced depression of SE was nearly 2.7-fold greater in diabetic mice at 2h than in non-diabetic mice. Examination of peritoneal proinflammatory cytokine levels 2h after LPS administration showed that diabetic mice had 4-, 2.5- and 3.6-fold greater concentrations of IL-1beta, IL-6 and TNF-alpha, respectively, when compared to non-diabetic mice. Control of blood glucose levels with injected insulin in diabetic mice improved 2h post LPS-induced loss of SE by 3.9-fold. Interestingly, insulin given intracerebroventricularly to diabetic mice did not impact LPS-induced loss of SE but did increase basal SE 8, 12 and 24h later. Finally, administration of STZ to hyperglycemic/hyperinsulinemic db/db mice did not alter LPS-induced loss of SE. Taken together these findings indicate that mice with T1D have augmented loss of SE in response to LPS and this is due to hyperglycemia and not to insulin.
Lin
Keng-I
KI
Division of Nutritional Science, University of Illinois, Urbana, IL 61801, USA.
Johnson
Daniel R
DR
Freund
Gregory G
GG
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000502:physiology*; D006943:Hyperglycemia / Q000097:blood / Q000276:immunology* / Q000523:psychology; D007113:Immunity, Innate / Q000502:physiology*; D007328:Insulin / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012919:Social Behavior; D018709:Statistics, Nonparametric
D016207:Cytokines; D007328:Insulin; D008070:Lipopolysaccharides