Effect of real-life insulin pump with predictive low-glucose management use for 3 months: Analysis of the patients treated in a Japanese center.

AIMS/INTRODUCTION: In Japan, an insulin pump with predictive low-glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. MATERIALS AND METHODS: We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of "post-suspend hyperglycemia" with the 640G device. RESULTS: After changing to the 640G device, the percentage of time in hypoglycemia (glucose <50 mg/dL) significantly decreased from 0.39% (0-1.51%) to 0% (0-0.44%; P = 0.0407). The percentage of time in hyperglycemia (glucose >180 mg/dL) significantly increased from 25.53% (15.78-44.14%) to 32.9% (24.71-45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2-53.75%), but it was significantly lower, 2.78% (0-21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20-61.66%; P = 0.0063). CONCLUSIONS: Predictive low-glucose management is an effective tool for reducing hypoglycemia, but possibly elicits "post-suspend hyperglycemia." This information is useful for achieving better blood glucose control in the patients treated with PLGM.

Low p38 MAPK and JNK activation in cultured hepatocytes of DRH rats; a strain highly resistant to hepatocarcinogenesis.

DRH rats are a hepatocarcinogenesis-resistant strain isolated from hepatocarcinogenesis-sensitive Donryu rats, and the liver of DRH shows less histological damage and fewer/smaller neoplastic hepatic lesions by the treatment with hepatocarcinogens. To investigate the mechanism of the resistance, the properties of hepatocytes of DRH and Donryu were compared. In primary culture, DRH hepatocytes exhibited higher proliferation and less apoptosis than Donryu hepatocytes in the presence of EGF and insulin. However, such difference was not correlated to the degree of DNA damage associated with cell culture or cell cycle checkpoint function. Although the mitogen-activated protein kinases [EGF receptor (EGFR) and extracellular signal regulating kinases (ERK1/2)] were activated to the same degree, the stress-activated protein kinases [p38 mitogen-activated protein kinase (p38) and c-jun N-terminal kinase (JNK)] were activated to a lesser degree in the DRH hepatocytes. Treatment with 2-acetylaminofluorene (2-AAF) in vivo also resulted in less JNK and p38 activation in the DRH livers. Furthermore, apoptosis signal-regulating kinase 1 (ASK1) was inhibited by the lysate from the DRH but not by the Donryu hepatocytes. The low activation of the stress-activated protein kinases may be linked to the resistance to cellular stress, which may underlie the hepatocarcinogenesis-resistance in DRH rats.

Different growth capacity between infant and adult mouse hepatocytes in vitro correlates to the cyclin D1 level without relation to oxidative DNA damage.

BACKGROUND: Proliferating capacity of hepatocytes is rapidly decreased during growth into maturity, but its exact reason(s) are not well known. METHODS: Hepatocytes isolated from infant (10-14 days old) and adult (10-13 months old) B6C3F1 mice were cultivated in the medium containing epidermal growth factor and insulin. Proliferative capacity, apoptosis, morphological changes, cell cycle proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were compared between the two hepatocyte populations. RESULTS: Although adult hepatocytes rapidly underwent cellular crisis characterized by extended morphology and multiple nuclei without proliferation, infant hepatocytes could proliferate with less crisis. Cyclin D1 was much more abundant in the infant than adult cells, but there was no difference according to the expression of cdk4, cdk2, cyclin E and cdk inhibitors (p16(Ink4) (p16), p21(Cip1/Waf1) (p21) and p27(Kip1) (p27)). 8-OHdG became high soon after cultivation, while it rapidly went down after day 2 both in the infant and adult cells. CONCLUSIONS: The high growth capacity of infant hepatocytes in vitro was dependent on the cyclin D1 level, but there was no relation to 8-OHdG.

Hepatocytes derived from peripheral blood stem cells of granulocyte-colony stimulating factor treated F344 rats in analbuminemic rat livers.

BACKGROUND: hematopoietic stem cells (SCs) mobilized from the bone marrow (BM) into peripheral blood (PB) are reported to have ability to differentiate into various cell types. We investigated whether PB-SCs mobilized by treatment with granulocyte-colony stimulating factor (G-CSF) in normal rats can raise albumin-producing hepatocytes after transplantation within the liver of analbuminemic rats. MATERIALS AND METHODS: Fischer 344 rats (F344) were used as donors, and F344 congenic Nagase's analbuminemic rats (F344alb) as recipients. The donors were repeatedly treated with human recombinant G-CSF, and their PB mononuclear cells (MNCs) were infused into the portal veins of recipients immediately after 70% hepatectomy (PH). RESULTS: Although a few single and small clusters (less than five cells) of albumin positive (alb+) hepatocytes were seen in the livers of untreated F344alb and of the animals undergoing PH alone or transplantation of PB-MNCs with or without the prior G-CSF treatment, clusters consisting of more than 6 alb+ hepatocytes were only detected in the livers of recipients that received transplantation of mobilized PB-MNCs or BM-MNCs under the regenerating condition induced by PH. Sry3, a Y chromosome marker, could be detected corresponding to the alb+ clusters by in situ hybridization when male donors and female recipients were used. Moreover, normal albumin gene sequences were demonstrated in the microdissected alb+ clusters by polymerase chain reaction, and the serum albumin levels were elevated in the recipients. CONCLUSIONS: Hematopoietic SCs mobilized from BM into PB by the G-CSF treatment may raise hepatocyte colonies, when transplanted into regenerating livers.

Colonization of albumin-producing hepatocytes derived from transplanted F344 rat bone marrow cells in the liver of congenic Nagase's analbuminemic rats.

BACKGROUND/AIMS: We investigated whether bone marrow cells (BMCs) of normal rats can be transformed in albumin-producing hepatocytes in analbuminemic rat livers. METHODS: BMCs (2 x 10(7)) from F344 rats (F344) were infused via the portal vein into the livers of congenic Nagase's analbuminemic rats (F344alb) immediately after 70% hepatectomy (PH). Alternatively, F344alb were hematopoietically reconstituted with F344 BMCs by whole body irradiation and BMC transplantation before PH. The recipients were examined for albumin positive (alb +) hepatocytes and albumin mRNA in the livers as well as serum albumin levels 4 weeks later. Sry3 in situ hybridization was done for the livers of female F344alb that received male F344 BMCs. RESULTS: Livers of untreated F344alb contained a few single and double alb+hepatocytes, but these did not form clusters after PH. Clusters (>3 alb + hepatocytes) were detected in livers of the recipients which were transplanted with BMCs immediately after PH as well as the reconstituted F344alb with or without PH. Normal albumin mRNA was detected in the recipient livers, and serum albumin levels were increased. Sry3 was identified in the alb+clusters in the female recipients. CONCLUSIONS: Transplanted BMCs from normal rats can increase clusters of albumin-producing hepatocytes within the liver of analbuminemic rats.