title: Anti-diabetic effects of globin digest and its active ingredient Leu-Ser-Glu-Leu in ICR mice, streptozotocin-induced diabetic mice and KK-Ay mice.
abstract: OBJECTIVE
  Leu-Ser-Glu-Leu (LSEL) is the main active ingredient of globin digest (GD) that has an anti-diabetic effect. Here, we investigated the anti-diabetic effect of LSEL for the first time.
  
  
  METHODS
  The anti-diabetic effects of GD and LSEL in ICR mice, streptozotocin (STZ)-induced diabetic mice and KK-Ay mice were examined.
  
  
  RESULTS
  GD and LSEL suppressed the elevation of blood glucose in an oral glucose tolerance test (OGTT) in ICR mice, STZ-induced diabetic mice and KK-Ay mice as well as in an oral sucrose tolerance test in ICR mice and in an insulin tolerance test (ITT) in KK-Ay mice. GD and LSEL decreased the blood glucose levels in the basal state in STZ-induced diabetic mice and KK-Ay mice. Furthermore, GD and LSEL elevated the serum insulin levels in an OGTT in ICR mice and KK-Ay mice and promoted the use of insulin in an ITT in KK-Ay mice. GD and LSEL increased the translocation or expression of the glucose transporter 4 in the muscle of ICR mice, STZ-induced diabetic mice and KK-Ay mice and increased the expression of the uncoupling protein 2 (UCP2) in the muscle of ICR mice.
  
  
  CONCLUSIONS
  These results indicate that GD and LSEL control blood glucose through the promotion of glucose uptake in the muscle of the mice. The acceleration of glucose uptake by GD and LSEL may be controlled by the promotion of insulin secretion and the up-regulation of UCP2 expression. GD and LSEL seem to be useful for lowering the incidence of hyperglycemia.
authors.affiliation: MG Pharma Inc, 7-7-25 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nakaoka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasakawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakao
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Chunning
authors.initials: C
authors.lastname: Tong
authors.forename: Chizuko
authors.initials: C
authors.lastname: Fukuhama
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kagawa
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005914:Globins / Q000737:chemistry / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011755:Pyrophosphatases / Q000096:biosynthesis; D013395:Sucrose; D000071246:Uncoupling Protein 2
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C548536:leucyl-seryl-glutamyl-leucine; D013395:Sucrose; D005914:Globins; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D011755:Pyrophosphatases; C010357:guanosine-diphosphatase