Renal function and insulin resistance as determinants of plasma leptin levels in patients with NIDDM

Shoji, Tetsuo; Nishizawà, Yoshiki; Emoto, Masanori; Maekawa, Kiyoshi; Hiura, Yoshikazu; Tanaka, Shinji; Kawagishi, Takahiko; Okuno, Yasuhisa; Morii, Hirotoshi

doi:10.1007/s001250050733

Cited by 46 publications

(34 citation statements)

References 24 publications

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“…For the second experiment, eight subjects (age 23.4 Ϯ 0.6 yr, height 171.1 Ϯ 2.6 cm, weight 61.0 Ϯ 2.6 kg) were tested for a measurement of glucose uptake by using a hyperinsulinemic-euglycemic clamp, according to the method by DeFronzo et al (6), with the aid of a blood glucose monitoring and glucose-insulin infusion system (Artificial Pancreas model STG22; Nikkiso, Tokyo, Japan) (22,45). After an overnight fast, subjects arrived at a clinical research room in Kyoto University Hospital at 8:30 AM and were kept in the supine position with both knees extended.…”

Section: Subjectsmentioning

confidence: 99%

Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation

Hamada

Sasaki

Hayashi

et al. 2003

Journal of Applied Physiology

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. Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation. J Appl Physiol 94: 2107-2112, 2003. First published January 31, 2003 10.1152/japplphysiol.00486.2002There is considerable evidence to suggest that electrical stimulation (ES) activates glucose uptake in rodent skeletal muscle. It is, however, unknown whether ES can lead to similar metabolic enhancement in humans. We employed low-frequency ES through surface electrodes placed over motor points of quadriceps femoris muscles. In male subjects lying in the supine position, the highest oxygen uptake was obtained by a stimulation pattern with 0.2-ms biphasic square pulses at 20 Hz and a 1-s on-off duty cycle. Oxygen uptake was increased by approximately twofold throughout the 20-min stimulation period and returned to baseline immediately after stimulation. Concurrent elevation of the respiratory exchange ratio and blood lactate concentration indicated anaerobic glycogen breakdown and utilization during ES. Whole body glucose uptake determined by the glucose disposal rate during euglycemic clamp was acutely increased by 2.5 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 in response to ES and, moreover, remained elevated by 3-4 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 for at least 90 min after cessation of stimulation. Thus the stimulatory effect of ES on whole body glucose uptake persisted not only during, but also after, stimulation. Low-frequency ES may become a useful therapeutic approach to activate energy and glucose metabolism in humans. glucose transport; euglycemic clamp; exercise; insulin sensitivity; oxygen uptake PHYSICAL EXERCISE HAS PROFOUND effects on energy and fuel metabolism in contracting skeletal muscle. It is well established that exercise can directly activate glucose uptake in skeletal muscle by inducing translocation of GLUT-4 glucose transporters to the cell surface via an insulin-independent mechanism (contraction-stimulated glucose transport) (10,11,31,37,49). This phenomenon is considered responsible for the acute effect of exercise on glucose transport, with the majority of glucose being taken up by contracting skeletal muscle. In fact, contraction-stimulated GLUT-4 translocation is not impaired in insulin-resistant conditions such as Type 2 diabetes and obesity (25). Furthermore, the period after exercise is also characterized by a substantial increase in insulin sensitivity that leads to insulin-dependent GLUT-4 translocation and glucose transport as a local phenomenon restricted to exercised muscles (9, 13, 39, 40, 48a). Thus these insulin-independent and -dependent mechanisms of exercise have been widely utilized to prevent individuals from developing glucose intolerance and to improve glycemic control in patients with Type 2 diabetes.Clinically, electrical stimulation (ES) of muscle is useful as a modality of assisting muscle contraction for those who have difficulties in performing voluntary exercise. The use of ES has been traditionally employed for muscle strengthening, maintenance of muscle mass and strength, a...

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Section: Subjectsmentioning

confidence: 99%

Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation

Hamada

Sasaki

Hayashi

et al. 2003

Journal of Applied Physiology

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“…Finally, it is interesting to note that leptin also activates JAK\STAT [39]. Given that leptin might be associated with obesity and insulin resistance in patients with non-insulin-dependent diabetes mellitus [40] and that leptin receptors are present in the kidney [39], it remains to be studied whether leptin could be induced by AGE.…”

Section: Discussionmentioning

confidence: 99%

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

Huang

Guh

Hung

et al. 1999

Biochemical Journal

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Advanced glycation end product (AGE) is important in the pathogenesis of diabetic nephropathy, which is characterized by cellular hypertrophy/hyperplasia leading to renal fibrosis. However, the signal transduction pathways of AGE remain poorly understood. The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been associated with cellular proliferation in some extra-renal cells. Because interstitial fibroblast proliferation might be important in renal fibrosis, we studied the role of the JAK/STAT pathway in NRK-49F (normal rat kidney fibroblast) cells cultured in AGE/BSA and non-glycated BSA. We showed that AGE dose-dependently (10-200 μg/ml) increased cellular mitogenesis in NRK-49F cells at 5 and 7 days. However, cellular mitogenesis was unaffected by the simultaneous presence of BSA. Regarding the JAK/STAT pathway, AGE (100 μg/ml) induced tyrosine phosphorylation of JAK2 (but not JAK1, JAK3 or TYK2) at 15-60 min; it also induced the tyrosine phosphorylation of STAT1 and STAT3 at 1-2 h and 0.5-4 h respectively. Being a transcription factor, AGE also increased the DNA-binding activities of STAT1 and STAT3 AG-490 (a specific JAK2 inhibitor) (5 μM) inhibited tyrosine phosphorylation of JAK2 and the DNA-binding activities of STAT1 and STAT3. The same results were obtained by using specific ‘decoy’ oligodeoxynucleotides (ODNs) that prevented STAT1 and STAT3 from binding to DNA. Meanwhile, the STAT1 or STAT3 decoy ODN and AG-490 were effective in reversing AGE-induced cellular mitogenesis. We concluded that the JAK2-STAT1/STAT3 signal transduction pathway is necessary for AGE-induced cellular mitogenesis in NRK-49F cells.

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“…20,21 In humans, circulating leptin concentrations are related to the degree of renal function, assessed by 1aplasma creatinine. 22 In contrast, it has been recently reported that intact leptin is increased in patients with end-stage renal disease, although increased production may account for the high concentrations of leptin. 23 Serum leptin concentrations are markedly elevated in the patients with chronic renal failure and higher plasma insulin, than in those with lower plasma insulin concentrations.…”

Section: Introductionmentioning

confidence: 86%

“…40 Leptin receptor mRNA was detected in the liver of rodents 22,23 and the addition of leptin, increases hepatic cell proliferation. 41 It is possible that an increase in circulating leptin concentrations may partially work as the proliferation factor of hepatocellular carcinoma cells in LC patients.…”

Section: Leptin In Liver Cirrhosis H Shimizu Et Almentioning

confidence: 99%

True

1998

Int J Obes

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OBJECTIVE: Leptin, the ob gene product, is an anorexigenic peptide secreted from adipose tissue. However, the mechanism of leptin clearanceadegradation has not been well determined in humans. The present study was undertaken to examine a possible involvement of liver in determining circulating leptin concentrations in humans. SUBJECTS: In the present study 58 healthy control subjects and 68 patients with liver cirrhosis (LC) without any renal dysfunction were randomly included. METHOD: The serum immunoreactive leptin (IRL) concentrations relative to the body mass index (BMI) were determined. Serum IRL and estradiol (E 2 ) concentrations were assayed by radioimmunoassay (RIA). RESULTS: The correlations between the BMI and circulating IRL concentrations were all signi®cant in male healthy controls (M-C), male patients with LC (M-LC), female healthy controls (F-C) and female patients with LC (F-LC). Circulating IRL concentrations were signi®cantly higher than control in F-LC but not M-LC groups. The ratio of circulating IRL concentrations to the BMI was signi®cantly higher in the M-LC group than in the M-C group and also signi®cantly higher in the F-LC group than in the F-C group. The correlation between the IRLaBMI ratio and serum total bilirubin concentrations was signi®cant (r 0.417, P`0.05) in the M-LC group, but not in the F-LC group. There was no signi®cant correlation of the IRLaBMI ratio to serum E 2 or albumin concentrations in either M-LC or F-LC groups.CONCLUSION: The present data demonstrated that the rate of increase in circulating IRL concentrations with the BMI was higher in LC patients of both genders. Liver may play a role in determining circulating leptin levels.

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Renal function and insulin resistance as determinants of plasma leptin levels in patients with NIDDM

Cited by 46 publications

References 24 publications

Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation

Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

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