Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion.

PURPOSE: We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice. METHODS: In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured. RESULTS: The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels. CONCLUSIONS: High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

Potential predictors of susceptibility to occupational stress in Japanese novice nurses - a pilot study.

BACKGROUND: Occupational stress is a known factor behind employee resignations; thus, early identification of individuals prone to such stress is important. Accordingly, in this pilot study we evaluated potential predictors of susceptibility to occupational stress in Japanese novice nurses. METHODS: Forty-two female novice nurses at Kagoshima University Hospital were recruited for the study population. Each underwent physical health and urinary examinations, and completed a lifestyle questionnaire at the time of job entry. Each also completed a Brief Job Stress Questionnaire (BJSQ), related to mental health status, at job entry and 5 months post-entry. Psychological stress, somatic symptoms, and combined BJSQ scores were determined for each time point. RESULTS: All three stress condition scores had significantly decreased at 5 months post-entry, suggesting occupational stress. Systolic blood pressure (r = -0.324, p < 0.05) and urinary sodium (r = -0.313, p < 0.05) were significantly negatively correlated with combined BJSQ score at 5 months post-entry. Post-entry stress condition scores were significantly low in subjects reporting substantial 1-year body weight change (≤ ± 3 kg) and short times between dinner and bedtimes (≤2 h), though baseline stress condition scores were not. Urinary sodium concentration, 1-year body weight change, and pre-sleep evening meals were then targeted for multivariate analysis, and confirmed as independent explanatory variables for post-entry stress condition scores. CONCLUSIONS: One-year body weight change, times between dinner and bedtimes, and urinary sodium concentration are promising potential predictors of susceptibility to occupational stress, and should be further investigated in future research. TRIAL REGISTRATION: ISRCTN ISRCTN17516023. Retrospectively registered 7 December 2016.

[A case of renal Fanconi syndrome due to Bence Jones' protein K-type multiple myeloma].

A 60-year-old man, who had been treated for chronic kidney disease and chronic hepatitis B infection, was referred to our hospital following presentation with thoracic bone pain and exacerbation of proteinuria and hematu- ria. On admission, laboratory test results showed evidence of hypophosphatemia, glucosuria and elevated levels of both urinary NAG and 62MG.The patient was diagnosed with Fanconi syndrome based on findings indicating the presence of pan-aminoaciduria, elevated urinary excretion of uric acid and an increased phosphorus reabsorption rate. Furthermore, bone scintigraphy showed increased multiple symmetric uptake of radiotracer in both sides of the ribs, leading to the diagnosis"of hypoposphatemia-related osteomalacia with renal Fanconi syndrome. Urinary immunoelectrophoresis indicated the presence of K Bence Jones' protein (BJP). A bone marrow biopsy examina- tion showed that the plasma-to-cell ratio was less than 10%. However, the patient had over lg/day of proteinuria and suppression of serum IgM (18mg/dL) and was, therefore, diagnosed with multiple myeloma based on SWOG criteria. Light microscopic examination showed evidence of glomerulosclerosis, intimal thickness of interlobular arteries and acidophilic granular deposits in the cytoplasm of the proximal epithelial tubular cells. Immunofluores- cence indicated positive anti-K staining in these regions. Electron microscopic examination of the proximal tubular epithelial cells revealed the presence of numerous diamond-shaped and oval crystals, thought to be the K light chain of BJP. In general, cast nephropathy, light chain deposition disease (LCDD) and AL amyloidosis are recog- nized renal injuries caused by myeloma. However, there have been few clinical reports of Fanconi syndrome with multiple myeloma, such as the case study we have described here. In addition, histological examination of a biopsy sample provided further evidence of K BJP in the proximal epithelial tubular cells.

Comparison of dipstick and quantitative tests for proteinuria and hematuria in middle-aged, male Japanese employees: A single-center study.

BACKGROUND AND AIMS: The early and reliable detection of chronic kidney disease is important. In the present study, we aimed to compare the diagnostic results for proteinuria and hematuria between the dipstick test used in primary occupational health examinations and the quantitative tests used in more thorough examinations in clinics. METHODS: We conducted a single-center observational study of male staff (N = 573) at Kagoshima University who underwent a health examination in 2017. Both dipsticks and biochemical methods were used to assess proteinuria and hematuria. RESULTS: For the dipstick test, the sensitivity, specificity, and positive predictive value were 55.6%, 92.4% and 10.4% for proteinuria, and 64.3%, 98.3% and 66.7% for hematuria, respectively. Four participants for whom false-negative results were obtained using dipsticks for proteinuria, and two of these had 3+ urinary glucose. CONCLUSION: Qualitative tests for proteinuria and hematuria had low sensitivities and positive predictive values. Therefore, for the early and reliable detection of chronic kidney disease, the use of quantitative urine tests should be considered during occupational health examinations.

Food Intake and Core Body Temperature of Pups and Adults in a db Mouse Line Deficient in the Long Form of the Leptin Receptor without Misty Mutation.

Different involvement of leptin signaling in food intake (FI) and body temperature (BT) in pups and adults has been suggested. However, the leptin receptor (Lepr) long-form-deficient (db) mouse line has not been fully examined in pups. In the most available db mouse line, wild-type (WT) mice have a mutation in the dedicator of cytokinesis 7 gene, named misty, which was recently revealed to be involved in neuronal development. Therefore, we established a line of db mice without the misty mutation using natural mating. Adult (8 weeks of age) homozygous db/db mice displayed significantly higher core body weight (BW) and FI and significantly lower core BT than WT mice. However, postnatal (2 weeks of age) db/db mice displayed similar BW and milk intake and significantly lower core BT than WT mice. Correspondingly, adult and postnatal db/db mice exhibited altered mRNA levels of hypothalamic orexigenic and anorexigenic peptide in adults but not in pups. Additionally, db/db mice displayed significantly lower mRNA levels of brown adipose tissue uncoupling protein 1 at both ages. In conclusion, the db mouse line without the misty mutation clearly showed the different involvements of the Lepr long form in FI and BT in pups and adults.

Effects of Diets with Different Proportions of Protein/Carbohydrate on Retinal Manifestations in db Mice.

BACKGROUND/AIM: Diabetic nephropathy is aggravated by a higher intake of total protein. The effects of diets with different proportions of protein and carbohydrate on diabetic retinopathy in db mice, a type-2 diabetes animal model, were examined, as well as diabetic nephropathy. MATERIALS AND METHODS: Control and db mice at 5 weeks of age were fed the diets (% energy of protein/carbohydrate/fat; L-diet: 12/71/17; H-diet: 24/59/17) under ad libitum conditions and pair-feeding conditions for 6 weeks, respectively. RESULTS: Mice fed the H-diet showed significantly greater retinal thickness by optical coherence tomography, and lower mRNA levels of angiotensinogen. Comparing combinations of diets and genotypes, db-H mice showed significantly higher mRNA levels of angiotensin-converting enzyme, advanced glycosylation end product-specific receptor, and cluster of differentiation molecule 11b (a microglial marker) than db-L mice. CONCLUSION: Dietary protein and carbohydrate proportions influenced retinal manifestations, including retinal thickness and gene expression in control and diabetic mice.

Effects of Dietary and Lighting Conditions on Diurnal Locomotor Activity and Body Temperature in Microminipigs.

The effects of dietary and lighting conditions on diurnal rhythm of locomotor activity (LA) and body temperature (BT) using four adult male microminipigs were investigated. Different feeding times, diet and lighting conditions were applied sequentially for 3 weeks in each phase as follows: Phase I: Morning mealtime, normal diet, 12-h lights on; phase II: mealtime changed to afternoon; phase III: diet changed to high-fat diet; phase IV: lighting changed to 20-h on; and phase V: phase I repeated. LA was measured by an actigraph which was worn on the body of each pig. A BT recording module (Thermochron Type-SL) was implanted in the neck subcutaneously. Phase II increased BT compared with phase I. Phase III increased LA and BT compared with phase II. Phase IV increased LA compared with phase III. LA in phase V was higher compared with phase I. These results can be extrapolated to other diurnal animals such as humans. This study provides an example of the effects of diet and lighting on biological activities in microminipigs under low-invasive procedures measuring LA and BT, leading to low variations in these measures.

Diurnal Variation of Melatonin Concentration in the Cerebrospinal Fluid of Unanesthetized Microminipig.

BACKGROUND/AIM: The aim of this study was to develop a method for sequentially collecting cerebrospinal fluid (CSF) from an unanesthetized microminipig, which shares many physiological and anatomical similarities with humans, such as diurnality, and investigate the diurnal variation of melatonin concentration in the CSF. MATERIALS AND METHODS: A catheter was placed percutaneously into the subarachnoid space of an anesthetized animal, and the tip of the catheter was placed into the cisterna magna under X-ray. We then sequentially collected CSF at light-on and -off times from the unanesthetized animal for several weeks. After catheter placement, a period of one week or more was necessary to relieve the contamination of RBCs in the CSF. RESULTS: A higher melatonin level in the CSF was noted during lights-off time, and the level was higher than that in the serum. CONCLUSION: This model of sequential collection of CSF will contribute to research in brain functions.