title: Combined long-term caffeine intake and exercise inhibits the development of diabetic nephropathy in OLETF rats.
abstract: This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long-Evans Tokushima fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf + Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf + Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 wk of age. Pre- and posttreatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UEAlb). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf + Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UEAlb, following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage.NEW & NOTEWORTHYThe present study showed that caffeine administration alone and/or combined with exercise results in an improvement of diabetic nephropathy (DN), including an increase in creatinine clearance and urinary Na excretion, a decrease in urinary protein excretion, and in renal morphological findings. To our knowledge, there are no other studies showing that caffeine administration inhibits DN progression.
authors.affiliation: Department of Laboratory Medicine, The Jikei University School of Medicine, Nishi-shinbashi, Minato-ku, Tokyo, Japan; masatos@jikei.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Laboratory of Health and Sports Science, Department of Pharmacy, Nihon University, Narashinodai, Funabashi-shi, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shindo
authors.affiliation: Department of Pharmacognosy and Natural Medicines, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan; and.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacognosy and Natural Medicines, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan; and.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shirataki
authors.affiliation: Department of Physiology, Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Waki
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000097:blood; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002110:Caffeine; D003404:Creatinine
keywords: caffeine; diabetic nephropathy; exercise; renal function; urinary albumin