Neuronal Signaling in Islet Development and Function

Abstract PRL and placental lactogen (PL) stimulate β-cell proliferation and insulin gene transcription in isolated islets and rat insulinoma cells, but the roles of the lactogenic hormones in islet development and insulin production in vivo remain unclear. To clarify the roles of the lactogens in pancreatic development and function, we measured islet density (number of islets/cm2) and mean islet size, β-cell mass, pancreatic insulin mRNA levels, islet insulin content, and the insulin secretory response to glucose in an experimental model of lactogen resistance: the PRL receptor (PRLR)-deficient mouse. We then measured plasma glucose concentrations after ip injections of glucose or insulin. Compared with wild-type littermates, PRLR-deficient mice had 26–42% reductions (P < 0.01) in islet density and β-cell mass. The reductions in islet density and β-cell mass were noted as early as 3 wk of age and persisted through 8 months of age and were observed in both male and female mice. Pancreatic islets of PRLR-deficient mice were smaller than those of wild-type mice at weaning but not in adulthood. Pancreatic insulin mRNA levels were 20–30% lower (P < 0.05) in adult PRLR-deficient mice than in wild-type mice, and the insulin content of isolated islets was reduced by 16–25%. The insulin secretory response to ip glucose was blunted in PRLR-deficient males in vivo (P < 0.05) and in isolated islets of PRLR-deficient females and males in vitro (P < 0.01). Fasting blood glucose concentrations in PRLR-deficient mice were normal, but glucose levels after an ip glucose load were 10–20% higher (P < 0.02) than those in wild-type mice. On the other hand, the glucose response to ip insulin was normal. Our observations establish a physiologic role for lactogens in islet development and function.

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Islet organoid as a promising model for diabetes

Protein & Cell ◽

10.1007/s13238-021-00831-0 ◽

2021 ◽

Author(s):

Xiaofei Zhang ◽

Zhuo Ma ◽

Eli Song ◽

Tao Xu

Keyword(s):

Stem Cell ◽

Disease Model ◽

Morphological Structure ◽

Great Promise ◽

Disease Models ◽

Human Organ ◽

Islet Development ◽

Autologous Islet Transplantation ◽

And Function

AbstractStudies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.

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Review for "Expression profiling of precuneus layer III cathepsin D‐immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability"

10.1002/cne.24929/v2/review1 ◽

2020 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Expression Profiling ◽

Cathepsin D ◽

Pyramidal Neurons ◽

Neuronal Signaling

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Conformation of Ribosomes from Escherichia Coli

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051062 ◽

1974 ◽

Vol 32 ◽

pp. 210-211

Author(s):

M. Boublik ◽

W. Hellmann ◽

F. Jenkins

Keyword(s):

Binding Sites ◽

Ribosomal Proteins ◽

Fluorescent Dyes ◽

Protein Biosynthesis ◽

Three Dimensional ◽

Spatial Arrangement ◽

Dimensional Structure ◽

Complete Understanding ◽

And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

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The Effect of Oxidized Cholesterol on the Aorta of Rabbits- Scanning Electron Microscopic Observations

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100054327 ◽

1982 ◽

Vol 40 ◽

pp. 340-341

Author(s):

S. K. Pena ◽

C. B. Taylor ◽

J. Hill ◽

J. Safarik

Keyword(s):

Cholesterol Biosynthesis ◽

Cholesterol Content ◽

Arterial Injury ◽

Electron Microscopic ◽

Aortic Smooth Muscle ◽

Oxidized Cholesterol ◽

Initial Event ◽

Membrane Structure And Function ◽

Scanning Electron Microscopic ◽

And Function

Introduction: Oxidized cholesterol derivatives have been demonstrated in various cell cultures to be very potent inhibitors of 3-hvdroxy-3- methylglutaryl Coenzyme A reductase which is a principle regulator of cholesterol biosynthesis in the cell. The cholesterol content in the cells exposed to oxidized cholesterol was found to be markedly decreased. In aortic smooth muscle cells, the potency of this effect was closely related to the cytotoxicity of each derivative. Furthermore, due to the similarity of their molecular structure to that of cholesterol, these oxidized cholesterol derivatives might insert themselves into the cell membrane, alter membrane structure and function and eventually cause cell death. Arterial injury has been shown to be the initial event of atherosclerosis.

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