The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice

Background & Aims

In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragliflozin on NASH in mice.

Methods

We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM. AMLN mice were fed an AMLN diet for 20 weeks. SGLT2I mice were fed an AMLN diet for 12 weeks and an AMLN diet with 40 mg ipragliflozin/kg for 8 weeks.

Results

AMLN mice showed steatosis, inflammation, and fibrosis in the liver as well as obesity and insulin resistance, features that are recognized in human NASH. Ipragliflozin improved insulin resistance and liver injury. Ipragliflozin decreased serum levels of free fatty acids, hepatic lipid content, the number of apoptotic cells, and areas of fibrosis; it also increased lipid outflow from the liver.

Conclusions

Ipragliflozin improved the pathogenesis of NASH by reducing insulin resistance and lipotoxicity in NASH-model mice. Our results suggest that ipragliflozin has a therapeutic effect on NASH with T2DM.     

Systematics and biogeography of the ant genus Crematogaster Lund subgenus Orthocrema Santschi in Asia (Hymenoptera: Formicidae)

The subgenus Orthocrema of the ant genus Crematogaster is a well defined group and diverse in the tropical Asia. Its systematics has remained poorly understood because of a lack of modern revisionary work. Crematogaster (Orthocrema) is revised for the Asian region, and 27 species including ten new species are recognized. Five species groups: the C. baduvi group (4 spp.); the C. binghamii group (3 spp.); the C. biroi group (10 spp.); the C. moatensis group (1 sp.); the C. quadriruga group (9 spp.) are established based on worker caste morphology. A key to Asian species of the subgenus Orthocrema based on the worker caste is given. Phylogenetic relationships of Asian Orthocrema are analyzed. The analysis revealed that the C. baduvi‐, C. binghamii‐, and C. biroi groups are monophyletic, and that the allopatric distribution patterns of closely related species imply that Asian Orthocrema is composed of relatively young taxa. There have been at least three west‐to‐east dispersal events across Wallace's line in the C. baduvi‐, C. quadriruga‐ and C. biroi groups. © 2016 The Linnean Society of London     

Effect of prey density on sex ratio of two predacious mites, Phytoseiulus persimilis and Amblyseius womersleyi (Acari: Phytoseiidae)

The sex ratios of two phytoseiid mites, Phytoseiulus persimilis and Amblyseius womersleyi, were observed under various prey conditions. Upon consumption of abundant prey, both phytoseiids produced progeny in a female-biased sex ratio (approximately 0.8 females). When few prey were consumed, the sex ratio was lowered to 0.5 (the unbiased sex ratio). Under the conditions in which the unbiased sex ratio was observed, male and female progeny appeared in an alternating sequence. To determine the change in the sex ratio and the sequence of progeny, the size of eggs deposited by females under various prey conditions was first compared. Survivorship and developmental rate of progeny (immatures) hatched under ample and poor prey conditions were also examined. The eggs deposited under poor prey conditions were smaller than those deposited under ample prey conditions. This is an indication that the phytoseiid females did not invest extra energy into the eggs to secure survival of their progeny under poor prey conditions. The male and female progeny from the small eggs developed slowly, probably due to the small egg size. However, hatchability of the small eggs and survival of the immatures were the same as those of the normal eggs when the immatures were reared under ample prey conditions. The immature survivorship was little affected by the prey consumption rate of their mothers when the immatures were reared under poor prey conditions. We concluded that the sex ratio of phytoseiid mites is not determined by the characteristics of the progeny, but by the nutritious condition of the females.Exp Appl Acarol 22: 709723 © 1998 Kluwer Academic Publishers     

Isolation of a Drosophila Gene Encoding a Head-Specific Guanylyl Cyclase

Abstract: We have isolated and characterized a new guanylyl cyclase gene ( dgcl) in Drosophila. The deduced amino acid sequence (683 amino acids) most closely resembled the mammalian solubletype guanylyl cyclase α subunit. The cyclase catalytic domain was highly conserved between the mammalian and Drosophila guanylyl cyclases. The dgcl mRNA was detected in wild-type heads but not in bodies, and its level was reduced in the mutant eyes absent (eya) , indicating that dgcl is preferentially expressed in the CNS and in the eye. The enriched distribution in the eye suggests that dgcl may have a role in phototransduction.     

Detection of hypoxia in the pulmonary tissues of Xenopus laevis over repeated dives

The oxygen environment in African clawed frogs (Xenopus laevis) continuously changes during their development, which involves a rapid increase in the body size, metamorphosis, and transition to adulthood. Nevertheless, there are limited reports on experimental models that are available for studying fluctuations in the oxygen environment in X. laevis. Thus, this study aimed to develop an experimental model on intermittent hypoxia in X. laevis and evaluate hypoxia and oxidative stress in the same. X. laevis were submerged in water with a dissolved oxygen concentration of 2 mg/L for 30 min; they were then removed from the water and allowed to freely absorb oxygen for 5 min. Immunostaining of pimonidazole-containing frozen tissue sections of the lung and liver using anti-pimonidazole antibodies as the hypoxia probes revealed that more than 95% of the submerged X. laevis cells were pimonidazole positive, providing direct evidence of tissue hypoxia. When the amount of oxidative stress in the lungs and liver was evaluated in terms of the amount of lipid peroxides, the diving group showed a 2.08-fold and 3.20-fold increase over the normal group, respectively. Following hypoxia exposure, the dry-to-wet weight ratios of the lung tissues was 1.27 times higher (p < .05), while the liver tissues was 1.06 times higher (although not significant). Thus, the degree of damage depended on the tissues affected. In the future, we believe that this model will be a promising option for analyzing the physiological responses of X. laevis to hypoxia and oxidative stress.     

Purification and Properties of an Extracellular Endo-1,4-r{beta}-Glucanase from Suspension-Cultured Poplar Cells

An endo-1,4-rß-glucanase (EC 3.2.1.4 [EC] ) was purifiedto apparent homogeneity from the culture medium of poplar (Populusalba L.) cells by sequential anion-exchange, hydrophobic, andgel-filtration chromatography. The preparation of extracellularrß-glucanase was homogeneous on SDS-polyacrylamidegel electrophoresis (PAGE) and native PAGE. The molecular weight,as determined by SDS-PAGE was 50,000, whereas that determinedby gel filtration was 40,000. The isoelectric point (pI) was5.5. The purified enzyme catalyzed the endohydrolysis of carboxy-methylcellulosewith a pH optimum of 6.0 and a k_m of 1.0 mg ml^–1. Theenzyme specifically cleaved the 1,4-rß-glucosyl linkagesof carboxymethylcellulose, swollen cellulose, lichenan and xyloglucan,although the last was hydrolyzed more slowly than the othertested substrates. The activity of the endo-1,4-rß-glucanaseincreased up to the early stage of the mid-logarithmic phaseof growth and then decreased rapidly, suggesting that the rß-glucanaseis induced before cell development. (Received April 28, 1993; Accepted July 19, 1993)     

Purification and Properties of an Auxin-Binding Protein from the Shoot Apex of Peach Tree

A soluble auxin-binding protein was purified from the shootapices of peach trees by chromatography on columns of CM-Toyopearl,Sephacryl S-200, 2,4-D-linked-Sepharose 4B and ConA-Sepharose.The molecular mass of the purified protein was estimated tobe about 100 kDa. After electrophoresis on a denaturing gel,the protein gave a single band with a molecular mass of 20 kDa.From Scatchard analyses, the dissociation constant for 2,4-Dwas calculated to be 4.1 10^–5 M and the specific bindingof 2,4-D at saturating concentration was 42 nmol (mg protein)^–1.The binding of [¹⁴C]-2,4-D to the protein was reversible andwas inhibited by IAA, 1-naphthylacetic acid and p-chlorophenoxyisobutyricacid. (Received June 25, 1992; Accepted October 20, 1992)     

Partial Purification of a Soluble Gibberellin-Binding Protein from Mung Bean Hypocotyls

A soluble binding protein specific for GA₄, GA₇ and GA₉ waspartially purified from mung bean hypocotyls, and its characteristicswere examined. Affinity chromatography using immobilized GA₃coupled to Sepharose 4B via the C-7 carboxyl group was veryeffective for purification of the protein. The molecular weightof the protein in its native state was estimated to be 150–200kDa by gel-permeation chromatography. This protein may be aheterooligomer consisting of two subunits (23 kDa and 35 kDa).The optimum pH for binding of GA₄ to the protein was around6.0 and the apparent dissociation constant (K_d) was 310^-7 M. (Received April 24, 1992; Accepted December 16, 1992)