- Brooklyn, NY, United States
Gladys Teitelman
SUNY: Downstate Medical Center, Cell Biology, Faculty Member
Research Interests: Biology, Cell Biology, Biological Chemistry, Medicine, Gene expression, and 15 moreBiological Sciences, DNA, Cell line, Humans, Insulin, Glucagon, Animals, CHEMICAL SCIENCES, HeLa cells, Enhancer, Base Sequence, DNA binding proteins, islets of Langerhans, binding sites, and Medical and Health Sciences
Research Interests: Molecular Biology, Biology, Immunohistochemistry, Medicine, Molecular endocrinology, and 15 moreBiological Sciences, DNA, Molecular, Insulin, Mice, Animals, Insulinoma, Cell nucleus, Amino Acid Sequence, Base Sequence, islets of Langerhans, Molecular Sequence Data, Cricetinae, endoderm, and Medical and Health Sciences
The XlHbox 8 homeodomain protein of Xenopus and STF-1, its mammalian homolog, are selectively expressed by β cells of adult mouse pancreatic islets, where they are likely to regulate insulin expression. We sought to determine whether the... more
The XlHbox 8 homeodomain protein of Xenopus and STF-1, its mammalian homolog, are selectively expressed by β cells of adult mouse pancreatic islets, where they are likely to regulate insulin expression. We sought to determine whether the expression of the homeobox protein/s during mouse embryonic development was specific to β cells or, alternatively, whether XlHbox 8/STF-1 protein/s were initially expressed by multipotential precursors and only later became restricted to the insulin-containing cells. With two antibodies, we studied the localization of STF-1 during murine pancreatic development. In embryos, as in adults, STF-1 was expressed by most β cells, by subsets of the other islet cell types and by mucosal epithelial cells of the duodenum. In addition, most epithelial cells of the pancreatic duct and exocrine cells of the pancreas transiently contained STF-1. We conclude that in mouse, STF-1 not only labels a domain of intestinal epithelial cells but also provides a spatial and...
Research Interests:
The observation that the two active forms of proprotein convertase 1/3 (PC1/3) were differentially expressed in beta cells of normal islets raised the possibility that this heterogeneity is lost during type 1 diabetes (T1D) progression.... more
The observation that the two active forms of proprotein convertase 1/3 (PC1/3) were differentially expressed in beta cells of normal islets raised the possibility that this heterogeneity is lost during type 1 diabetes (T1D) progression. To test this hypothesis, the expression of the convertase was evaluated by confocal microscopy in sections of human pancreas of autoantibody positive (AA+) and T1D donors and compared with that of control. Islets of T1D pancreas were comprised of beta cells expressing either low or high PC1/3 levels and all islets of a pancreatic section contained only one beta cell type. Pancreata of AA+ donors contained either of these two classes of islets intermixed with normal islets comprised of beta cells with heterogeneous PC1/3 expression. This alteration affected the expression of proinsulin and insulin, which in most AA+ and T1D donors were lower than in controls. The present results indicate that the heterogeneity of PC1/3 expression is lost in all beta c...
Research Interests:
Supplemental material, DS_10.1369_0022155419831641 for Heterogeneous Expression of Proinsulin Processing Enzymes in Beta Cells of Non-diabetic and Type 2 Diabetic Humans by Gladys Teitelman in Journal of Histochemistry & Cytochemistry
Research Interests:
Research Interests:
Research Interests:
Precursors of the neurons that populate enteric ganglia cannot be recognized morphologically when they first enter the gut; therefore embryonic gut in culture, explanted before neurons appear, develops a myenteric plexus that contains... more
Precursors of the neurons that populate enteric ganglia cannot be recognized morphologically when they first enter the gut; therefore embryonic gut in culture, explanted before neurons appear, develops a myenteric plexus that contains cholinergic and serotonergic neurons. The evidence indicates that the developing gut maintains an immature proliferating pool of neuronal precursors that may tentatively and transiently express a given neuronal phenotype. Catecholaminergic expression is an example of such a transient phenotype. It is possible that sequential changes, occurring as a function of gestational age in the enteric neuronal microenvironment and interacting with this persistent pool of neuronal precursors, are responsible for the generation of enteric neuronal diversity. The sequential appearance of the various types of enteric neuron is consistent with this hypothesis. The persistence of a dividing cell population may also be linked to the generation of the large number of enteric neurons.
Research Interests:
Research Interests:
Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry.... more
Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry. The majority of these neurons localized to area X of Rexed contact ependyma. Thus, spinal AADC neurons have the enzymatic capacity to catalyze directly the conversion of the amino acids tyrosine, tryptophan, or phenylalanine to their respective amines tyramine, tryptamine, or phenylethylamine. These amines normally present in the central nervous system may be of potential clinical significance as endogenous psychotomimetics.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Endocrinology, Biology, Medicine, In Situ Hybridization, Biological Sciences, and 15 moreCell line, Cell Differentiation, Internal Medicine, Glucagon, Mice, Animals, Early development, Hyperplasia, Enzyme, Cell Proliferation, Embryos, Gene Expression Regulation, Alpha cell, Differential expression, and Medical and Health Sciences
Pancreatic islets are enveloped by a sheath of Schwann cells, the glial cells of the peripheral nervous system (PNS). The fact that Schwann cells of the PNS become reactive and express nerve growth factor (NGF) and other growth factors... more
Pancreatic islets are enveloped by a sheath of Schwann cells, the glial cells of the peripheral nervous system (PNS). The fact that Schwann cells of the PNS become reactive and express nerve growth factor (NGF) and other growth factors following axotomy suggested the possibility that peri-islet Schwann cells could become activated by islet injury. To test this hypothesis, we examined two animal models of islet injury. The first model was mice and rats injected with streptozotocin (SZ), a specific beta-cell toxin. The second model was NOD mice, a strain in which beta cells are deleted by an autoimmune process. We found that peri-islet Schwann cells became reactive following islet injury and began to express increased levels of NGF and the neurotrophin receptor p75. Lesions to the pancreas also markedly induced NGF expression by exocrine and endocrine cells. Neurotrophin expression was not unique to adult tissues since pancreatic cells transiently expressed p75, the NGF receptor Trk A, and NGF during development. These observations suggest that NGF could play an important role in pancreas during embryogenesis and in processes leading to repair following islet injury in adults.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The catecholamine-synthesizing enzymes, tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase were examined by immunohistochemistry in hypertrophied paraganglia of aged male Fischer-344 rats. All... more
The catecholamine-synthesizing enzymes, tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase were examined by immunohistochemistry in hypertrophied paraganglia of aged male Fischer-344 rats. All paraganglionic cells reacted with antibodies against tyrosine hydroxylase. Dopamine beta-hydroxylase was identified in most paraganglionic cells, indicating that they synthesized norepinephrine. A variable number of paraganglia were positive for phenylethanolamine-N-methyltransferase, which suggested that they synthesized epinephrine. The formaldehyde-induced fluorescence method demonstrated greenish-yellow fluorescence or yellowish-brown fluorescence. The intensity of the fluorescence was in the same range as in adrenal medullary cells. The observations indicate that paraganglia are capable of synthesizing epinephrine.
Research Interests:
The islet cells of the mammalian pancreas are comprised of four different endocrine cell types, each containing a specific hormone. Islet cells also contain two enzymes of the catecholamine biosynthetic pathway : tyrosine hydroxylase (TH)... more
The islet cells of the mammalian pancreas are comprised of four different endocrine cell types, each containing a specific hormone. Islet cells also contain two enzymes of the catecholamine biosynthetic pathway : tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). The cell lineage relationships of these different cell types have not been examined and it is not known whether, during development, they originate from the same or from different precursor populations. In this study we used immunocytochemical procedures to determine whether developing pancreatic cells express markers common to endocrine and exocrine cell types. We found that acinar cell precursors express AADC prior to the appearance of an exocrine marker and that the expression of AADC in acinar cells persists throughout embryogenesis to the first month of postnatal life. At this time, acinar cells do not contain AADC. We also found that exocrine cells containing AADC never express other islet-cell markers. These findings suggest that while acinar and islet cells both arise from precursor cells containing AADC, these progenitor cells do not express a combined endocrine-exocrine phenotype.
Research Interests:
Research Interests:
Research Interests:
Purpose Connective tissue growth factor (CTGF) is a profibrotic factor that induces extracellular matrix (ECM) production and angiogenesis, two processes involved in diabetic retinopathy (DR). In this study, we examined whether insulin... more
Purpose Connective tissue growth factor (CTGF) is a profibrotic factor that induces extracellular matrix (ECM) production and angiogenesis, two processes involved in diabetic retinopathy (DR). In this study, we examined whether insulin therapy or a CTGF-specific small interfering RNA (siRNA) administered to diabetic rats decreased the levels of CTGF and of selected putative downstream genes in the retina. Methods Rats with streptozotocin-induced diabetes were used. Animals received either no treatment for 12 weeks or were administered constant insulin therapy. MRNA and protein levels of CTGF and select ECM genes were determined using real-time PCR and western blotting of the retina. Localization of CTGF in the retina was visualized using immunohistochemistry. A group of diabetic rats received intravitreal injection of CTGF siRNA, and the retinas were examined three days later. Results CTGF mRNA and protein significantly increased in the retinas of diabetic rats. Immunohistochemistry...
Research Interests:
Gonadal inversion produced by sex hormones has been studied by many authors trying to understand sex differentiation and its hormonal control. The work of Dantchakoff (1935), Wolff & Ginglinger (1935) and Willier, Gallagher & Koch (1935),... more
Gonadal inversion produced by sex hormones has been studied by many authors trying to understand sex differentiation and its hormonal control. The work of Dantchakoff (1935), Wolff & Ginglinger (1935) and Willier, Gallagher & Koch (1935), who studied sex inversion in genetically male chick gonads caused by the action of estrogens, as well as work done since then on birds and other vertebrates, dealt with the morphology of inverted gonads, while very few attempts have been made to analyse them functionally. Perhaps the most important work on this aspect has been that of Wolff & Haffen (1961), who demonstrated that inverted chick gonads are capable of producing feminizing substances. It seems well established that hormonal production by normal chick embryonic ovaries is localized in medullary interstitial cells as judged from their high content in lipids and cholesterol (Scheib, 1959; Narbaitz & Sabatini, 1963) and δ5–3β- hydroxysteroid dehydrogenase (Narbaitz & Kolodny, 1964; Chieffi...
Research Interests:
In pancreatic beta cells, proinsulin (ProIN) undergoes folding in endoplasmic reticulum/Golgi system and is translocated to secretory vesicles for processing into insulin and C-peptide by the proprotein convertases (PC)1/3 and PC2, and... more
In pancreatic beta cells, proinsulin (ProIN) undergoes folding in endoplasmic reticulum/Golgi system and is translocated to secretory vesicles for processing into insulin and C-peptide by the proprotein convertases (PC)1/3 and PC2, and carboxypeptidase E. Human beta cells show significant variation in the level of expression of PC1/3, the critical proconvertase involved in proinsulin processing. To ascertain whether this heterogeneity is correlated with the level of expression of the prohormone and mature hormone, the expression of proinsulin, insulin, and PC1/3 in human beta cells was examined. This analysis identified a human beta cell type that expressed proinsulin but lacked PC1/3 (ProIN+PC1/3−). This beta cell type is absent in rodent islets and is abundant in human islets of adults but scarce in islets from postnatal donors. Human islets also contained a beta cell type that expressed both proinsulin and variable levels of PC1/3 (ProIN+PC1/3+) and a less abundant cell type that...
Research Interests:
Although there is evidence indicating transcriptional and functional heterogeneity in human beta cells, it is unclear whether this heterogeneity extends to the expression level of the enzymes that process proinsulin to insulin in beta... more
Although there is evidence indicating transcriptional and functional heterogeneity in human beta cells, it is unclear whether this heterogeneity extends to the expression level of the enzymes that process proinsulin to insulin in beta cells. To address this question, the expression levels of prohormone convertases (PC) 1/3, proprotein convertase 2 (PC2), and carboxypeptidase E (CPE) were determined in immune-stained sections of human pancreas. In non-diabetic donors, the level of proprotein convertase 1/3 (PC1/3) expression varied among beta cells of each islet but the average per islet was similar for all islets of each donor. Although the average PC1/3 expression of all islets examined per sample was unique for each pancreas, donors had similar levels of proinsulin/insulin expression. PC2 expression in beta cells showed less pronounced inter- and intraislet variation while CPE levels were fairly constant. The relationship between PC1/3 and PC2 expression levels was variable among ...
Research Interests:
Research Interests: Neuroscience, Biology, Medicine, Autonomic Nervous System, Mice, and 15 moreAnimals, Phenotype, Norepinephrine, Intestines, Digestive System, Foetus, Rat, Autoradiography, Gastrointestinal Tract, Fetus, Cell Proliferation, Catecholamines, Differential expression, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests:
Publisher Summary The availability of immunological and molecular probes to identify the various hormones has provided new tools to examine the mechanisms that govern the differentiation of pancreatic islet cells. From the perspective of... more
Publisher Summary The availability of immunological and molecular probes to identify the various hormones has provided new tools to examine the mechanisms that govern the differentiation of pancreatic islet cells. From the perspective of a developmental biologist, the fundamental questions regarding the endocrine pancreas revolve around the role of genetic and epigenetic signals on differentiation of islet cells and on stability and/or plasticity of the differentiated phenotype. This chapter examines recent advances on these issues and describes the areas that remain to be explored. It describes the studies that relied on immunohistochemical techniques used to visualize one or more antigens in the same tissue sections. In other instances, immunohistochemistry was combined with autoradiography.
Research Interests:
Research Interests: Biology, Biological Chemistry, Medicine, Biological Sciences, Insulin, and 14 moreMice, Animals, Peptides, Phenotype, CHEMICAL SCIENCES, Tamoxifen, Protease Inhibitors, Oral Hypoglycemic Agents, Cell Proliferation, Venoms, Recombinant Proteins, Glucose Intolerance, Selective estrogen receptor modulators, and Medical and Health Sciences
Research Interests:
In the adult mouse, pancreatic islets contain four islet cell types: alpha, beta, delta and pancreatic polypeptide cells that synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. The early progenitor cells... more
In the adult mouse, pancreatic islets contain four islet cell types: alpha, beta, delta and pancreatic polypeptide cells that synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. The early progenitor cells to the pancreatic islets are multipotential and coactivate all the islet-specific genes from the time they first appear. As development proceeds, expression of islet-specific hormones becomes restricted to the pattern of expression characteristic of mature islet cells. The phenotype of mature islet cells, however, is not stable since different environmental stimuli can induce the reappearance of embryonal traits in mature beta cells.
Research Interests:
The search for new sources of β cells is driven by the shortage of islets of Langerhans suitable for replacement therapy for type I diabetes. Recent advances in stem cell research, described in other sections of this book, have led to... more
The search for new sources of β cells is driven by the shortage of islets of Langerhans suitable for replacement therapy for type I diabetes. Recent advances in stem cell research, described in other sections of this book, have led to promising sources of insulin-producing cells ...
Research Interests:
In embryonic mice, the catecholamine biosynthetic enzyme tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] can be visualized immunocytochemically in a population of cells in... more
In embryonic mice, the catecholamine biosynthetic enzyme tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] can be visualized immunocytochemically in a population of cells in epithelial cords of the developing pancreas. These embryonic catecholamine cells, first seen by day 11, are large and vacuolated and have a folded nuclear membrane. One day later, at day 12, glucagon is first detected immunocytochemically in pancreatic cells similar in location and morphology to the embryonic catecholamine cells. By use of a method for detecting both antigens in the same cell, both the hydroxylase and glucagon can be visualized between day 12 and day 14 in 10-40% of stained cells. From day 14, the number of cells stained for hydroxylase decreases; they cannot be detected after day 18. In contrast, the cells containing glucagon increase during development and persist throughout life. Endocrine cells of the embryonic pancreas also contain ...
Research Interests:
Research Interests:
The development of endocrine cell types within the pancreas is thought to involve the progressive restriction of pluripotential stem cells, which gives rise to the four major cell types: insulin-, glucagon-, somatostatin-, and pancreatic... more
The development of endocrine cell types within the pancreas is thought to involve the progressive restriction of pluripotential stem cells, which gives rise to the four major cell types: insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-expressing cells. The mechanism by which these peptide hormone genes are induced and then either maintained or repressed during development is unknown, but their coexpression in early precursor cells suggests the involvement of common regulatory factors. Here we show that the somatostatin transcription factor STF-1 is also a principal regulator of insulin expression in beta-cells of the pancreas. STF-1 stimulates the insulin gene by recognizing two well defined islet-specifying elements on the insulin promoter and by subsequently synergizing in trans with the juxtaposed helix-loop-helix protein E47. Within the STF-1 protein, an N-terminal trans-activation domain functions cooperatively with E47 to stimulate insulin transcription. As truncated STF-1 polypeptides lacking the N-terminal activation domain strongly inhibit insulin promoter activity in beta-islet cells, our results suggest that the specification of islet cell types during development may be in part determined by the expression of STF-1 relative to other islet cell factors.
Research Interests: Biology, Immunohistochemistry, Transcription Factors, Molecular endocrinology, Gene expression, and 14 moreWestern blotting, Biological Sciences, DNA, Molecular, Insulin, Mice, Animals, Cell nucleus, Pax, DNA binding proteins, islets of Langerhans, Pancreatic islets, Drug synergism, and Medical and Health Sciences
It has been shown that inhibition of de novo sphingolipid synthesis increases insulin sensitivity. For further exploration of the mechanism involved, we utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2 (... more
It has been shown that inhibition of de novo sphingolipid synthesis increases insulin sensitivity. For further exploration of the mechanism involved, we utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2 ( Sptlc2 ) gene knockout mice and sphingomyelin synthase 2 ( Sms2 ) gene knockout mice. SPT is the key enzyme in sphingolipid biosynthesis, and Sptlc2 is one of its subunits. Homozygous Sptlc2 -deficient mice are embryonic lethal. However, heterozygous Sptlc2 -deficient mice that were viable and without major developmental defects demonstrated decreased ceramide and sphingomyelin levels in the cell plasma membranes, as well as heightened sensitivity to insulin. Moreover, these mutant mice were protected from high-fat diet-induced obesity and insulin resistance. SMS is the last enzyme for sphingomyelin biosynthesis, and SMS2 is one of its isoforms. Sms2 deficiency increased cell membrane ceramide but decreased SM levels. Sms2 deficiency also increased insul...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
To date, the role of pancreatic hormones in pancreatic islet growth and differentiation is poorly understood. To address this issue, we examined mice with a disruption in the gene encoding prohormone convertase 2 (PC2). These mice are... more
To date, the role of pancreatic hormones in pancreatic islet growth and differentiation is poorly understood. To address this issue, we examined mice with a disruption in the gene encoding prohormone convertase 2 (PC2). These mice are unable to process proglucagon, prosomatostatin, and other neuroendocrine precursors into mature hormones. Initiation of insulin (IN) expression during development was delayed in PC2 mutant mice. Cells containing IN were first detected in knockout embryos on d 15 of development, 5 d later than in wild-type littermates. However, the IN+ cells of d 15 PC2 mutant mice coexpressed glucagon, as did the first appearing β-cells of controls. In addition, lack of PC2 perturbed the pattern of expression of transcription factors presumed to be involved in the determination of the mature α-cell phenotype. Thus, in contrast to controls, α-cells of mutant mice had protracted expression of Nkx 6.1 and Pdx-1, but did not express Brn-4. Islets of adult mutant mice also ...
Research Interests: Endocrinology, Cell Division, Biological Sciences, Cell Differentiation, Pregnancy, and 15 moreMice, Female, Animals, Male, Hyperplasia, Transcription Factor, Age Factors, Cell Proliferation, Embryos, Proprotein Convertase, Cell Volume, islets of Langerhans, Knock Out Mice, Pancreatic islets, and Medical and Health Sciences
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the... more
Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2(-/-)), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr(-/-)). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling.