title: Pertussis toxin administered spinally induces a hypoglycemic effect on normal and diabetic mice.
abstract: OBJECTIVE
  To show whether intrathecal (i.t.) treatment with pertussis toxin (PTX) produces a hypoglycemic effect in ICR, db/db and streptozotocin-treated mice.
  
  
  METHODS
  The blood glucose level (BGL) was measured after i.t. treatment with PTX, AB5 toxins and PTX subunits. Insulin or leptin levels were measured after PTX injection. The effect of PTX on the BGL was examined in adrenalectomized (ADX) mice. Glucose transporter (GLUT) levels were determined by Western blotting.
  
  
  RESULTS
  PTX attenuated the elevated BGL in the D-glucose-fed model in a long-term manner. Heat-labile toxin (HLT), HLT subunit B or Shiga toxin, which belong to the AB5 toxins, administered i.t. did not affect the BGL. PTX A protomer (PTX-A) or PTX B oligomers (PTX-B) injected i.t. did not have an effect on the BGL as well. However, combined treatment with PTX-A and PTX-B subunits caused a hypoglycemic effect. The leptin level was gradually reduced by PTX for up to 6 days, without affecting the insulin level. PTX administered i.t. significantly decreased the BGL further in ADX mice. Moreover, GLUT-2 (hypothalamus and pituitary gland), GLUT-4 (muscle) and GLUT-3 (adrenal gland) expression levels were increased, whereas GLUT-1 (brain cortex, liver, muscle and spinal cord), GLUT-2 (liver) and GLUT-3 (brain cortex and pituitary gland) expression levels were decreased.
  
  
  CONCLUSIONS
  Our data suggest that PTX administered spinally produces a hypoglycemic effect in a long-term manner, and PTX-induced hypoglycemia appears to be mediated by the reduction in activity of the glucocorticoid system. Furthermore, PTX may modulate the insulin level during hypoglycemia. Among GLUTs, GLUT-4 in muscle, GLUT-2 in the liver, hypothalamus and pituitary gland as well as GLUT-1 in the adrenal gland may be responsible for PTX-induced hypoglycemia.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Lim
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.forename: Jin-Koo
authors.initials: JK
authors.lastname: Lee
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000494:pharmacology*; D013311:Streptozocin; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D013311:Streptozocin; D037342:Pertussis Toxin