title: Therapeutic impact of leptin on diabetes, diabetic complications, and longevity in insulin-deficient diabetic mice.
abstract: OBJECTIVE
  The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse.
  
  
  METHODS
  We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Akita mice with physiological hyperleptinemia (LepTg:Akita). Metabolic parameters were monitored for 10 months. Pair-fed studies and glucose and insulin tolerance tests were performed. The pancreata and kidneys were analyzed histologically. The plasma levels and pancreatic contents of insulin and glucagon, the plasma levels of lipids and a marker of oxidative stress, and urinary albumin excretion were measured. Survival rates were calculated.
  
  
  RESULTS
  Akita mice began to exhibit severe hyperglycemia and hyperphagia as early as weaning. LepTg:Akita mice exhibited normoglycemia after an extended fast even at 10 months of age. The 6-h fasting blood glucose levels in LepTg:Akita mice remained about half the level of Akita mice throughout the study. Food intake in LepTg:Akita mice was suppressed to a level comparable to that in WT mice, but pair feeding did not affect blood glucose levels in Akita mice. LepTg:Akita mice maintained insulin hypersensitivity and displayed better glucose tolerance than did Akita mice throughout the follow-up. LepTg:Akita mice had normal levels of plasma glucagon, a marker of oxidative stress, and urinary albumin excretion rates. All of the LepTg:Akita mice survived for >12 months, the median mortality time of Akita mice.
  
  
  CONCLUSIONS
  These results indicate that leptin is therapeutically useful in the long-term treatment of insulin-deficient diabetes.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Naito
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Fumiko
authors.initials: F
authors.lastname: Miyanaga
authors.forename: Hideki
authors.initials: H
authors.lastname: Yokoi
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Cheol
authors.initials: C
authors.lastname: Son
authors.forename: Masashi
authors.initials: M
authors.lastname: Mukoyama
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000172:deficiency / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D010179:Pancreas / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D005934:Glucagon