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University of Massachusetts Medical School

Cellular and Molecular Physiology

Insulin

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Full-Text Articles in Life Sciences

Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers Mar 2018

Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers

Open Access Articles

Many patients with type 1 diabetes (T1D) have residual beta cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual beta cells and alpha cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced, and these cells had alterations in transcription factors constituting alpha and ...


Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu Jan 2018

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu

GSBS Dissertations and Theses

Proper functioning of endocrine cells is crucial for organismal homeostasis. The underlying mechanisms that fine-tune the amount, and the timing of hormone secretion are not clear. JIP1 / MAPK8IP1 (JNK interacting protein 1) is a scaffold protein that mediates cellular stress response, and is highly expressed in endocrine cells, including insulin secreting b-cells in pancreas islets. However, the role of JIP1 in b-cells is unclear. This study demonstrates that b-cell specific Jip1 ablation results in decreased glucose-induced insulin secretion, without a change in Insulin1 and Insulin2 gene expression. Inhibition of both JIP1-kinesin interaction, and JIP1-JNK interaction by genetic mutations also resulted ...


Systemic Insulin Sensitivity Is Regulated By Gps2 Inhibition Of Akt Ubiquitination And Activation In Adipose Tissue, Carly T. Cederquist, Claudia Lentucci, Camila Martinez Calejman, Vanessa Hayashi, Joseph Orofino, David A. Guertin, Susan K. Fried, Mi-Jeong Lee, M. Dafne Cardamone, Valentina Perissi Jan 2017

Systemic Insulin Sensitivity Is Regulated By Gps2 Inhibition Of Akt Ubiquitination And Activation In Adipose Tissue, Carly T. Cederquist, Claudia Lentucci, Camila Martinez Calejman, Vanessa Hayashi, Joseph Orofino, David A. Guertin, Susan K. Fried, Mi-Jeong Lee, M. Dafne Cardamone, Valentina Perissi

Open Access Articles

OBJECTIVE: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT.

METHODS: The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice).

RESULTS ...


Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe Oct 2016

Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe

GSBS Dissertations and Theses

Obesity is the top risk factor for the development of type 2 diabetes mellitus in humans. Obese adipose tissue, particularly visceral depots, exhibits an increase in macrophage accumulation and is described as being in a state of chronic low-grade inflammation. It is characterized by the increased expression and secretion of inflammatory cytokines produced by both macrophages and adipocytes, and is associated with the development of insulin resistance. Based on these observations, we investigated the potential role of macrophage infiltration on whole body metabolism, using genetic and diet-induced mouse models of obesity.

Using flow cytometry and immunofluorescence imaging we found that ...


Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina Distefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech Jul 2016

Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina Distefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech

Open Access Articles

Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced beta cell mass, fewer proliferating beta cells and reduced islet-specific gene mRNA expression compared ...


A Role For Tnmd In Adipocyte Differentiation And Adipose Tissue Function: A Dissertation, Ozlem Senol-Cosar Jun 2016

A Role For Tnmd In Adipocyte Differentiation And Adipose Tissue Function: A Dissertation, Ozlem Senol-Cosar

GSBS Dissertations and Theses

Adipose tissue is one of the most dynamic tissues in the body and is vital for metabolic homeostasis. In the case of excess nutrient uptake, adipose tissue expands to store excess energy in the form of lipids, and in the case of reduced nutrient intake, adipose tissue can shrink and release this energy. Adipocytes are most functional when the balance between these two processes is intact. To understand the molecular mechanisms that drive insulin resistance or conversely preserve the metabolically healthy state in obese individuals, our laboratory performed a screen for differentially regulated adipocyte genes in insulin resistant versus insulin ...


Role Of Protein Kinase Map4k4 In Energy Metabolism: A Dissertation, Laura V. Danai Apr 2015

Role Of Protein Kinase Map4k4 In Energy Metabolism: A Dissertation, Laura V. Danai

GSBS Dissertations and Theses

Systemic glucose regulation is essential for human survival as low or chronically high glucose levels can be detrimental to the health of an individual. Glucose levels are highly regulated via inter-organ communication networks that alter metabolic function to maintain euglycemia. For example, when nutrient levels are low, pancreatic α-cells secrete glucagon, which signals to the liver to promote glycogen breakdown and glucose production. In times of excess nutrient intake, pancreatic β-cells release insulin. Insulin signals to the liver to suppress hepatic glucose production, and signals to the adipose tissue and the skeletal muscle to take up excess glucose via insulin-regulated ...