Hans-Ewald Hohmeier

Journal Article J Clin Invest · January 16, 2024 Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and ... Full text Open Access Link to item Cite

Identification of a small molecule that stimulates human β-cell proliferation and insulin secretion, and protects against cytotoxic stress in rat insulinoma cells.

Journal Article PLoS One · 2020 A key event in the development of both major forms of diabetes is the loss of functional pancreatic islet β-cell mass. Strategies aimed at enhancing β-cell regeneration have long been pursued, but methods for reliably inducing human β-cell proliferation wi ... Full text Link to item Cite

Improving human β-cell maturation in vitro.

Journal Article Nat Cell Biol · February 2019 Full text Link to item Cite

Delayed apoptosis allows islet β-cells to implement an autophagic mechanism to promote cell survival.

Journal Article PLoS One · 2017 Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerabl ... Full text Link to item Cite

A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.

Journal Article Mol Cell Biol · December 1, 2016 The homeodomain transcription factor Pdx-1 has important roles in pancreas and islet development as well as in β-cell function and survival. We previously reported that Pdx-1 overexpression stimulates islet cell proliferation, but the mechanism remains unc ... Full text Link to item Cite

Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in Rodent and Human Pancreatic β-Cells.

Journal Article Mol Endocrinol · September 2015 Better understanding how glucagon-like peptide 1 (GLP-1) promotes pancreatic β-cell function and/or mass may uncover new treatment for type 2 diabetes. In this study, we investigated the potential involvement of microRNAs (miRNAs) in the effect of GLP-1 on ... Full text Link to item Cite

Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency.

Journal Article J Clin Invest · August 3, 2015 Rare functional variants of ankyrin-B have been implicated in human disease, including hereditary cardiac arrhythmia and type 2 diabetes (T2D). Here, we developed murine models to evaluate the metabolic consequences of these alterations in vivo. Specifical ... Full text Link to item Cite

Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.

Journal Article Proc Natl Acad Sci U S A · April 8, 2014 Loss of functional β-cell mass is a hallmark of type 1 and type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor NK6 homeobox 1 (Nkx6.1) in rat pancreatic ... Full text Link to item Cite

Pdx-1 activates islet α- and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2.

Journal Article Mol Cell Biol · October 2013 The homeodomain transcription factor Pdx-1 has important roles in pancreatic development and β-cell function and survival. In the present study, we demonstrate that adenovirus-mediated overexpression of Pdx-1 in rat or human islets also stimulates cell rep ... Full text Link to item Cite

Control of voltage-gated potassium channel Kv2.2 expression by pyruvate-isocitrate cycling regulates glucose-stimulated insulin secretion.

Journal Article J Biol Chem · August 9, 2013 Recent studies have shown that the pyruvate-isocitrate cycling pathway, involving the mitochondrial citrate/isocitrate carrier and the cytosolic NADP-dependent isocitrate dehydrogenase (ICDc), is involved in control of glucose-stimulated insulin secretion ... Full text Link to item Cite

The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of insulin and somatostatin release from pancreatic islets.

Journal Article J Pharmacol Exp Ther · February 2013 The voltage-gated potassium channels Kv2.1 and Kv2.2 are highly expressed in pancreatic islets, yet their contribution to islet hormone secretion is not fully understood. Here we investigate the role of Kv2 channels in pancreatic islets using a combination ... Full text Link to item Cite

A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function.

Journal Article Cell Metab · July 3, 2012 Deterioration of functional islet β-cell mass is the final step in progression to Type 2 diabetes. We previously reported that overexpression of Nkx6.1 in rat islets has the dual effects of enhancing glucose-stimulated insulin secretion (GSIS) and increasi ... Full text Link to item Cite

Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis.

Journal Article PLoS One · April 6, 2011 UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf11 ... Full text Link to item Cite

Cholinergic augmentation of insulin release requires ankyrin-B.

Journal Article Sci Signal · March 16, 2010 Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. ... Full text Link to item Cite

Increased insulin sensitivity in mice lacking collectrin, a downstream target of HNF-1alpha.

Journal Article Mol Endocrinol · June 2009 Collectrin is a downstream target of the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha), which is mutated in maturity-onset diabetes of the young subtype 3 (MODY3). Evidence from transgenic mouse models with collectrin overexpression in ... Full text Link to item Cite

Agenesis of the dorsal pancreas and associated diseases.

Journal Article Dig Dis Sci · March 2009 BACKGROUND: Agenesis of the dorsal pancreas is a very rare congenital pancreatic malformation and is associated with some other diseases. METHODS: A PubMed search revealed 53 cases of agenesis of the dorsal pancreas. RESULTS: In 28 patients with this conge ... Full text Link to item Cite

Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets.

Journal Article J Biol Chem · October 24, 2008 We have previously demonstrated a role for pyruvate cycling in glucose-stimulated insulin secretion (GSIS). Some of the possible pyruvate cycling pathways are completed by conversion of malate to pyruvate by malic enzyme. Using INS-1-derived 832/13 cells, ... Full text Link to item Cite

Stimulation of human and rat islet beta-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1.

Journal Article Mol Cell Biol · May 2008 The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic islet beta-cell development, but its effects on adult beta-cell function, survival, and proliferation are not well understood. In the present study, we demonstrated that trea ... Full text Link to item Cite

Trefoil factor 3 stimulates human and rodent pancreatic islet beta-cell replication with retention of function.

Journal Article Mol Endocrinol · May 2008 Both major forms of diabetes involve a decline in beta-cell mass, mediated by autoimmune destruction of insulin-producing cells in type 1 diabetes and by increased rates of apoptosis secondary to metabolic stress in type 2 diabetes. Methods for controlled ... Full text Link to item Cite

Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents.

Journal Article Mol Endocrinol · March 2007 Recent advances in functional genomics afford the opportunity to interrogate the expression profiles of thousands of genes simultaneously and examine the function of these genes in a high-throughput manner. In this study, we describe a rational and efficie ... Full text Link to item Cite

Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology.

Journal Article Proc Natl Acad Sci U S A · May 30, 2006 This study describes a method of gene delivery to pancreatic islets of adult, living animals by ultrasound targeted microbubble destruction (UTMD). The technique involves incorporation of plasmids into the phospholipid shell of gas-filled microbubbles, whi ... Full text Link to item Cite

Pro- and antiapoptotic proteins regulate apoptosis but do not protect against cytokine-mediated cytotoxicity in rat islets and beta-cell lines.

Journal Article Diabetes · May 2006 Type 1 diabetes results from islet beta-cell death and dysfunction induced by an autoimmune mechanism. Proinflammatory cytokines such as interleukin-1beta and gamma-interferon are mediators of this beta-cell cytotoxicity, but the mechanism by which damage ... Full text Link to item Cite

Islets for all?

Journal Article Nat Biotechnol · October 2005 Full text Link to item Cite

Cell lines derived from pancreatic islets.

Journal Article Mol Cell Endocrinol · December 30, 2004 The islets of Langerhans play a major role in control of metabolic fuel homeostasis. The rapid increase in incidence of diabetes worldwide has spurred renewed interest in islet cell biology. However, gaining a detailed understanding of islet function at a ... Full text Link to item Cite

Enhanced cAMP protein kinase A signaling determines improved insulin secretion in a clonal insulin-producing beta-cell line (INS-1 832/13).

Journal Article Mol Endocrinol · September 2004 In type 2 diabetes, beta-cells become glucose unresponsive, contributing to hyperglycemia. To address this problem, we recently created clonal insulin-producing cell lines from the INS-1 insulinoma line, which exhibit glucose responsiveness ranging from po ... Full text Link to item Cite

Understanding of basic mechanisms of beta-cell function and survival: prelude to new diabetes therapies.

Journal Article Cell Biochem Biophys · 2004 Type 1 and type 2 diabetes are both diseases of insulin insufficiency, although they develop by distinct pathways. The recent surge in the incidence of type 2 diabetes and the chronic ailments confronted by patients with either form of the disease highligh ... Full text Link to item Cite

Inflammatory mechanisms in diabetes: lessons from the beta-cell.

Journal Article Int J Obes Relat Metab Disord · December 2003 Inflammation plays an important role in the destruction of pancreatic islet beta-cells that leads to type I diabetes. This involves infiltration of T-cells and macrophages into the islets and local production of inflammatory cytokines such as interleukin ( ... Full text Link to item Cite

Discrete and complementary mechanisms of protection of beta-cells against cytokine-induced and oxidative damage achieved by bcl-2 overexpression and a cytokine selection strategy.

Journal Article Diabetes · June 2003 We have been investigating the potential utility of engineered cell lines as surrogates for primary islet cells in treatment of type 1 diabetes. To this end, two strategies that have emerged for procuring cell lines with resistance to immune-mediated damag ... Full text Link to item Cite

Expression of the transcription factor STAT-1 alpha in insulinoma cells protects against cytotoxic effects of multiple cytokines.

Journal Article J Biol Chem · January 5, 2001 Destruction of pancreatic islet beta-cells in type 1 diabetes appears to result from direct contact with infiltrating T-cells and macrophages and exposure to inflammatory cytokines such as interferon (IFN)-gamma, interleukin (IL)-1 beta, and tumor necrosis ... Full text Link to item Cite

Selection of insulinoma cell lines with resistance to interleukin-1beta- and gamma-interferon-induced cytotoxicity.

Journal Article Diabetes · April 2000 Engineered insulinoma cell lines may represent an alternative to isolated islets for transplantation therapy of type 1 diabetes. Success of this approach may require development of cell lines that can withstand cytokine-mediated damage. To this end, we hav ... Full text Link to item Cite

Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion.

Journal Article Diabetes · March 2000 The biochemical mechanisms involved in regulation of insulin secretion are not completely understood. The rat INS-1 cell line has been used to gain insight in this area because it secretes insulin in response to glucose concentrations in the physiological ... Full text Link to item Cite

Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production.

Journal Article J Clin Invest · May 1, 1998 The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic effects of inflammatory cytokines represents a potential hinderance to the use of such cells for transplantation therapy of insulin-dependent diabetes mellitus (IDDM). In the ... Full text Link to item Cite

Engineered cell lines for insulin replacement in diabetes: current status and future prospects.

Journal Article Diabetologia · July 1997 The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas tr ... Full text Link to item Cite

Regulation of insulin secretion from novel engineered insulinoma cell lines.

Journal Article Diabetes · June 1997 In the accompanying article, we describe the creation of novel cell lines derived from RIN 1046-38 rat insulinoma cells by stable transfection with combinations of genes encoding human insulin, GLUT2, and glucokinase. Herein we describe the regulation of i ... Full text Link to item Cite

Insulinsezernierende Zellen zur Therapie des Diabetes mellitus

Journal Article Naturwissenschaften · December 1, 1996 Even with intensive insulin therapy it is impossible to reach physiological blood glucose levels in insulin-dependent diabetes mellitus. Because of the high costs and technical problems involved in islet cell transplantation broad applicability of this the ... Cite

[Insulin producing cells as therapy in diabetes mellitus].

Journal Article Naturwissenschaften · January 1996 Even with intensive insulin therapy it is impossible to reach physiological blood glucose levels in insulin-dependent diabetes mellitus. Because of the high costs and technical problems involved in islet cell transplantation broad applicability of this the ... Link to item Cite

[Studies on human porin. V. The expression of "porin31HL" in the plasmalemma is not by cell transformation].

Journal Article Biol Chem Hoppe Seyler · August 1991 In recent papers we proved "Porin 31HL" to be located on the surface of human, EBV-transformed B lymphocytes. Here we present proof of "Porin 31HL" in the plasmalemma of normal human blood lymphocytes. For this purpose B and T lymphocytes were isolated fro ... Link to item Cite

Studies on human porin. V. The expression of "porin31HL" in the plasmalemma is not by cell transformation

Journal Article Biological Chemistry Hoppe-Seyler · 1991 In recent papers we proved "Porin 31HL" to be located on the surface of human, EBV-transformed B lymphocytes. Here we present proof of "Porin 31HL" in the plasmalemma of normal human blood lymphocytes. For this purpose B and T lymphocytes were isolated fro ... Cite