Improved glucose metabolism by Eragrostis tef potentially through beige adipocyte formation and attenuating adipose tissue inflammation.

BACKGROUND: Teff is a staple food in Ethiopia that is rich in dietary fiber. Although gaining popularity in Western countries because it is gluten-free, the effects of teff on glucose metabolism remain unknown. AIM: To evaluate the effects of teff on body weight and glucose metabolism compared with an isocaloric diet containing wheat. RESULTS: Mice fed teff weighed approximately 13% less than mice fed wheat (p < 0.05). The teff-based diet improved glucose tolerance compared with the wheat group with normal chow but not with a high-fat diet. Reduced adipose inflammation characterized by lower expression of TNFα, Mcp1, and CD11c, together with higher levels of cecal short chain fatty acids such as acetate, compared with the control diet containing wheat after 14 weeks of dietary treatment. In addition, beige adipocyte formation, characterized by increased expression of Ucp-1 (~7-fold) and Cidea (~3-fold), was observed in the teff groups compared with the wheat group. Moreover, a body-weight matched experiment revealed that teff improved glucose tolerance in a manner independent of body weight reduction after 6 weeks of dietary treatment. Enhanced beige adipocyte formation without improved adipose inflammation in a body-weight matched experiment suggests that the improved glucose metabolism was a consequence of beige adipocyte formation, but not solely through adipose inflammation. However, these differences between teff- and wheat-containing diets were not observed in the high-fat diet group. CONCLUSIONS: Teff improved glucose tolerance likely by promoting beige adipocyte formation and improved adipose inflammation.

Crystallization and preliminary X-ray analysis of rat SHPS-1.

SHPS-1, a receptor-type transmembrane protein, is abundantly expressed in neural and myeloid tissues. The most amino-terminal immunoglobulin-like domain of SHPS-1 plays an important role in a variety of cell functions by binding its ligand CD47. Interaction between SHPS-1 and CD47 is thought to be involved in negative regulation of phagocytosis. The ligand-binding domain of rat SHPS-1 was purified and crystallized using the vapour-diffusion method with the solution-stirring technique. Preliminary X-ray diffraction data were collected from SHPS-1 crystals to 2.8 A resolution and reduced to primitive hexagonal space group P622. Unit-cell parameters are a = b = 100.5, c = 101.3 A.

Enhanced gastric emptying of a liquid gastric load in mice lacking cholecystokinin-B receptor: a study of CCK-A,B, and AB receptor gene knockout mice.

BACKGROUND: Although cholecystokinin (CCK) has been shown to inhibit gastric emptying via CCK-A receptors (CCK-ARs), the role of CCK-B receptors (CCK-BRs) has not been verified. We examined whether gastric emptying of a nonnutrient liquid load was modified in CCK-AR, BR, and ARBR gene knockout mice. METHODS: A liquid gastric load prepared with phenol red was administered via an orogastric tube (0.15 ml/mouse). The animals were killed by decapitation, and gastric emptying was estimated at 10 and 30 min after ingestion. The effects of the sulfated form of CCK-8 (CCK-8S) and of graded doses of atropine were examined. In addition, a proton pump inhibitor was administered to wild-type mice to examine the contribution of gastric acid to emptying. RESULTS: Gastric emptying was significantly enhanced in mice lacking CCK-BR, as compared with wild-type and CCK-AR(-/-) mice. CCK-8S inhibited gastric emptying in mice with CCK-AR, but not in mice without CCK-AR. A proton pump inhibitor did not affect gastric emptying. Atropine dose dependently inhibited gastric emptying in all genotypes. The thickness of smooth muscle was comparable for all genotypes. CONCLUSIONS: The gastric emptying of a nonnutrient liquid load was enhanced in mice without CCK-BR, although the precise mechanism is not known. Although cholecystokinin (CCK) has been shown to inhibit gastric emptying via CCK-A receptors (CCK-ARs), the role of CCK-B receptors (CCK-BRs) has not been verified. We examined whether gastric emptying of a nonnutrient liquid load was modified in CCK-AR, BR, and ARBR gene knockout mice.

Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation.

Two closely related casein kinase I (CKI) isoforms, CKIdelta and CKIepsilon, are ubiquitously expressed in many human tissues, but their specific biologic function remains to be clarified. Here, we provide the first evidence that CKIepsilon is involved in hematopoietic cell differentiation. CKIepsilon, but not CKIdelta, was down-regulated along with human granulocytic differentiation. The specific down-regulation was observed in granulocyte colony-stimulating factor (G-CSF)-induced cell differentiation of murine interleukin-3 (IL-3)-dependent myeloid progenitor 32D cells. Introduction of wild-type (WT)-CKIepsilon into 32D cells inhibited the G-CSF-induced cell differentiation, whereas kinase-negative (KN)-CKIepsilon promoted the differentiation. Neither WT- nor KN-CKIepsilon affected IL-3-dependent cell growth. Moreover, introduction of WT- or KN-CKIdelta did not affect the cytokine-induced cell growth and differentiation. While G-CSF-induced activation of signal transducers and activators of transcription 3 (STAT3) was sustained by KN-CKIepsilon, STAT3 activation was attenuated by WT-CKIepsilon. This may be explained by the fact that the suppressor of cytokine signaling 3 (SOCS3) was stabilized by its physical association with CKIepsilon. Such stabilization by CKIepsilon was also seen in IL-3-induced beta-catenin. The stabilization of downstream components of cytokine and Wnt signaling by CKIepsilon might be critical for integration of several intracellular signaling pathways to a cell-specific biologic response in hematopoietic cell self-renewal.

Reduced anxious behavior in mice lacking the CCK2 receptor gene.

Cholecystokinin 2 (CCK2) receptors have been implicated as mediators of anxiety in standard mouse models such as exploratory behavior both in black and white test boxes and in elevated plus-mazes. We investigated the role of the CCK2 receptor in anxiety by evaluating the behavior of mice lacking the gene for this receptor in these standard anxiety models (i.e., exploratory behavior in a black and white test box and exploratory behavior in an elevated plus-maze). In the black and white test box, mice lacking the CCK2 receptor gene showed significantly increased numbers of transitions between the boxes compared to control mice. In the elevated plus-maze, mice lacking the CCK2 receptor gene displayed significantly more head dips than control mice. These results suggest that mice lacking the CCK2 receptor gene are less anxious than normal mice.

Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze.

Cholecystokinin (CCK)-A receptor (AR) and B receptor (BR) share highly amino acid sequence homology and overlap in their tissue distribution. We examined the anxiety-related behavior of CCK-AR, CCK-BR, and CCK-ARBR gene knockout (-/-) mice in the elevated plus-maze. CCK-AR(-/-) mice showed a significantly higher frequency of open-arm entries than wild-type and CCK-BR(-/-) mice, whereas the percentage open-arm entry values in CCK-AR(-/-) mice did not differ from those in wild-type mice. Thus, this increased frequency in open-arm entries for CCK-AR(-/-) mice was interpreted to be due to an increase in locomotor activity, rather than to a reduction in anxiety. By contrast, CCK-BR(-/-) mice showed significantly lower percentage open-arm entry values and spent significantly less time in the open- arms than wild-type and CCK-AR(-/-) mice. We therefore conclude that a lack of CCK-BR increases the anxiety-related behavior of the mouse in the elevated plus- maze.

Developmental expression of EphB6 in the thymus: lessons from EphB6 knockout mice.

A member of the largest family of receptor protein kinases, EphB6, lacks its intrinsic kinase activity, but it is expressed in normal human tissues. To investigate the physiological function of EphB6, we generated EphB6 deficient mice. EphB6(-/-) mice developed normally, revealed no abnormality in general appearance, and were fertile. Although a developmental increase of EphB6 in the fetal thymus was confirmed, T-cell development in various lymphoid organs of EphB6(-/-) mice was comparable to those of EphB6(+/+). Even in fetal thymus organ cultures, any developmental differences of EphB6(-/-) and EphB6(+/+) thymocytes were undetectable. The different binding characteristics to ephrin-Fc proteins between EphB6(-/-) and EphB6(+/+) thymocytes demonstrated that ephrin-B2 is the unique ligand for EphB6 among eight known ephrins. While EphB6 was a dominant receptor that binds to ephrin-B2 in adult thymocytes, fetal ones also expressed another EphB that binds to ephrin-B2. Overlapping expression of the EphB subfamily in the fetal thymus might compensate for the loss of EphB6 during the thymic development.

Energy metabolism and turnover are increased in mice lacking the cholecystokinin-B receptor.

Cholecystokinin (CCK) is an important gastrointestinal hormone as well as a neurotransmitter. Two types of CCK receptors, types A and B, have been identified. The CCK-A receptor is involved in satiety, food intake and behavior, whereas the B receptor is involved in anxiety. We recently produced CCK-A, -B and AB receptor knockout mice to study the role of these receptors in energy metabolism. Daily energy intake and expenditure were significantly greater in CCK-BR(-/-) and CCK-AR(-/-)BR(-/-) mice than CCK-AR(-/-) and wild-type [CCK-AR(+/+)BR(+/+)] mice. Relative liver and kidney weights (g/kg body) were significantly greater in CCK-AR(-/-)BR(-/-) mice than in wild-type mice. Energy metabolism and energy turnover were increased in mice with a disruption of the CCK-BR gene, although the underlying mechanism is unknown.

Plasma Proteins Case Report: Massive Bone Marrow Necrosis with Polyclonal Hypergammaglobulinemia and Blue Toe Syndrome.

Massive bone marrow necrosis was rare, and most of these cases were accompanied with malignant disease. We report a case that was thought to be idiopathic massive bone marrow necrosis. It was a 58 y.o. male who was admitted because of blue toe syndrome and hypergammaglobulinemia. We tried to detect malignant diseases with computed tomography and gallium scintigraphy, and infectious diseases with bacterial culture and viral antibodies, but all of them were negative. Pancytopenia and bone marrow necrosis was not improved, and he had died after 5-month hospitalization. Autopsy revealed massive bone marrow necrosis and bone marrow fibrosis after necrosis, but malignant or infectious diseases were not detected. It may be diagnosed as idiopathic massive bone marrow necrosis.