title: Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes.
abstract: BACKGROUND
  Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis.
  
  
  METHODS
  A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence.
  
  
  RESULTS
  Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated α isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of α, β, γ, and δ isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged.
  
  
  CONCLUSIONS
  Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.
authors: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors: Lejla
authors: L
authors: Ferhatovic
authors: Adriana
authors: A
authors: Banozic
authors: Sandra
authors: S
authors: Kostic
authors: Tina Ticinovic
authors: TT
authors: Kurir
authors: Anela
authors: A
authors: Novak
authors: Luka
authors: L
authors: Vrdoljak
authors: Marija
authors: M
authors: Heffer
authors: Damir
authors: D
authors: Sapunar
authors: Livia
authors: L
authors: Puljak
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D010146:Pain / Q000201:enzymology* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2