The role of insulin receptor substrate 2 in beta cell function

Insulin receptor substrate (Irs) 2 plays complex roles in the regulation of glucose homeostasis, energy balance and CNS development. To address the tissue-specific role of Irs2 signalling events, conditional Irs2-deficient mice were generated. IrsHoxAox mice were crossed with mice expressing Cre recombinase under the control of the rat insulin II gene promoter (RIPCre mice). Deletion of Irs2 occurred in pancreatic (3 cells and in a population of hypothalamic neurons thus generating RlPCrelrslKO mice. RlPCrelrs2KO mice displayed impaired glucose tolerance, reduced beta cell mass and islet number but remained hyperinsulinaemic. Over time some recovery in islet mass was seen with islets not expressing Cre repopulating the islets. Furthermore RlPCrelrslKO mice developed a prominent hypothalamic phenotype with hyperphagia, obesity, increased body length and hyperleptinaemia. RlPCrelrslKO mice were sensitive to leptin treatment and displayed a normal metabolic rate. Characterisation of the hypothalamic neurons that express Cre recombinase revealed that they did not express pro-opiomelanocortin or neuropeptide Y. These findings therefore demonstrate a critical role for intrinsic Irs2 signalling pathways in (3-cell and hypothalamic function and give insights into novel hypothalamic neuronal populations involved in the regulation of energy homeostasis. Deleting STAT3 in the same tissues (RIPCreSTATJKO) resulted in a mouse with no (3 cell phenotype but which developed obesity. This obesity was not due to hyperphagia and was possibly due to an increase in activity, although this has not been confirmed. In addition to this, RIPCreSTAT3KO mice were sensitive to leptin treatment. These findings therefore demonstrate that STAT3 signalling pathways are not needed for normal (3-cell mass and function but that STAT3 in the hypothalamus plays an important role in body weight maintenance

The role of insulin receptor substrate 2 in hypothalamic and β cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

The role of insulin receptor substrate 2 in hypothalamic and beta cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in beta cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and beta cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced P cell mass. Overt diabetes did not ensue, because beta cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced beta cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in beta cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

Discovery of a novel simian pegivirus in common marmosets (Callithrix jacchus) with lymphocytic enterocolitis

From 2010 to 2015, 73 common marmosets

Infant mental health home visiting therapists- reflective supervision self- efficacy in community practice settings

In recent years, there has been an increase in the research on reflective supervision, including the development of tools designed to measure reflective practice in the context of reflective supervision. The Reflective Supervision Self- Efficacy Scale for Supervisees (RSSESS) is a self- report measure that has been used in previous evaluations and is designed to assess perceived reflective practice self- efficacy for Infant Mental Health- Home Visiting (IMH- HV) therapists. Properties of the RSSESS including factor structure and reliability are explored in a first study that lays the foundation for the use of the RSSESS in an IMH- HV evaluation in the State of Michigan. IMH- HV therapists completed the RSSESS at 4 time points over a 12- month period and also completed a Clinician Profile Form that included questions about their IMH background and their work experience, including job satisfaction and burnout. Results indicated that the RSSESS is a reliable tool to measure change in reflective practice skills. IMH- HV therapists demonstrated growth in their use of reflective practice skills with families and their observational skills over the 12- month period. In addition, results indicated correlations between reflective supervision self- efficacy and job satisfaction as well as burnout.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154909/1/imhj21834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154909/2/imhj21834_am.pd