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Posts Tagged ‘Diabetes mellitus type 1’


Reported by:  Dr. Venkat S Karra. Ph.D.

Sticking yourself in the finger day after day: For many diabetics, this means of checking blood glucose is an everyday part of life. Especially for patients with Type-1 diabetes, who always have to keep a close eye on their levels, since their bodies are incapable of producing the insulin to break down the glucose in the blood. Several times a day, they have to place a tiny drop of blood on a test strip. It is the only way they can ascertain the blood glucose value, so they can inject the correct amount of insulin needed. And this pricking is not only a burdensome: it may also cause inflammation or cornification of the skin. And for pain-sensitive patients, the procedure is agony.

The daily sticking of the finger may soon become a thing of the past, thanks to a diagnostic system with Fraunhofer technology built-in. The underlying concept is a biosensor that is located on the patient’s body. It is also able to measure glucose levels continuously using tissue fluids other than blood, such as in sweat or tears. The patient could dispense with the constant needle pricks. In the past, such bioelectric sensors were too big, too imprecise and consumed too much power. Researchers at the Fraunhofer Institute for Microelectronic Circuits and Systems IMS in Duisburg have recently achieved a major breakthrough: They have developed a biosensor in nano-form that circumvents these hurdles.

Diagnostic system in miniature

The principle of measurement involves an electrochemical reaction that is activated with the aid of an enzyme. Glucose oxidase converts glucose into hydrogen peroxide (H2O2) and other chemicals whose concentration can be measured with a potentiostat. This measurement is used for calculating the glucose level. The special feature of this biosensor: the chip, measuring just 0.5 x 2.0 mm, can fit more than just the nanopotentiostat itself. Indeed, Fraunhofer researchers have attached the entire diagnostic system to it. “It even has an integrated analog digital converter that converts the electrochemical signals into digital data,” explains Tom Zimmermann, business unit manager at IMS. The biosensor transmits the data via a wireless interface, for example to a mobile receiver. Thus, the patient can keep a steady eye on his or her glucose level. “In the past, you used to need a circuit board the size of a half-sheet of paper,” says Zimmermann. “And you also had to have a driver. But even these things are no longer necessary with our new sensor.”

Durable biosensor

The minimal size is not the only thing that provides a substantial advantage over previous biosensors of this type. In addition, the sensor consumes substantially less power. Earlier systems required about 500 microamperes at five volts; now, it is less than 100 microamperes. That increases the durability of the system – allowing the patient to wear the sensor for weeks, or even months. The use of a passive system makes this durability possible. The sensor is able to send and receive data packages, but it can also be supplied with power through radio frequency.

The glucose sensor was engineered by the researchers at Noviosens, a Dutch medical technology firm. Since it can be manufactured so cost-effectively, it is best suited for mass production. These non-invasive measuring devices for monitoring blood glucose levels may become the basis for a particularly useful further development in the future: The biochip could control an implanted miniature pump that, based on the glucose value measured, indicates the precise amount of insulin to administer. That way, diabetes patients could say goodbye to incessant needle-pricks forever.

Source:

rdmag

Fraunhofer Institute

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Reporter: Aviva Lev-Ari, PhD, RN

Diabetes Drug Discovery and Beyond

October 1-3, 2012

Copley Marriott Hotel, Boston, MA

The Diabetes Drug Discovery and Beyond meeting will cover progress on promising pre-clinical and early clinical phase diabetes drug candidates. But this year, we will also highlight emerging therapeutic targets that probe how the underlying defects in metabolic diseases are connected. Some presentations will cover obesity, other metabolic disorders and cardiovascular disease in the context of diabetes and energy homeostasis.

TUESDAY, OCTOBER 2


TARGETS FOR NEW DIABETES THERAPIES

1:30 pm Chairperson’s Remarks

Claire Steppan, Ph.D., Associate Research Fellow, Diabetes, Pfizer

1:40 FEATURED SPEAKER

Targeting Diabetes via Glucocorticoid Modulation: The Identification of Advanced 11b-HSD-1 Inhibitors

Jeffrey RoblJeffrey A. Robl, Ph.D., Executive Director, Metabolic Diseases R&D, Bristol-Myers Squibb

Preventing excess glucocorticoid tone in metabolically active tissues such as the liver and adipose may be  beneficial in addressing glucose homeostasis and hyperglycemia in patients with type 2 diabetes. We have optimized a series of triazolopyridine based inhibitors resulting in the advancement of BMS-770767 to phase 2 clinical trials. The discovery of BMS-770767 will be presented as well as a description of its development  properties, pharmacokinetics, and pre-clinical pharmacology profile.

2:10 Dyslipidemia Targets and Diabetes

Rebecca Taub, M.D., CEO, Madrigal Pharmaceuticals

This talk will defining diabetic dyslipidemia and discuss how elevated VLDL, triglycerides and fatty liver might contribute to diabetic CV disease. Novel dyslipidemia mechanisms to treat diabetic dyslipidemia including THRbeta agonists will also be covered.

2:40 Effects of PF-04620110, a Novel Diacylglycerol Acyl-Transferase 1 (DGAT1) Inhibitor on Healthy-Obese Volunteers and Type 2 Diabetic Subjects

Claire Steppan, Ph.D., Associate Research Fellow, Diabetes, Pfizer

Inhibition of DGAT1, the terminal enzyme in the synthesis of triglycerides (TG), has been proposed for the treatment of type 2 diabetes (T2DM). We sought to examine the effects of a potent and selective DGAT1 inhibitor, PF-04620110, on vitamin A absorption, TG, glucose, insulin and total amide glucagon like peptide-1 (GLP-1) levels in both healthy-obese volunteers and Type 2 Diabetic subjects. The results of these studies will be presented.

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Pharmacological Manipulation of Diacyl Glycerol Acyl Transferase 1 Using Pre-Clinical Models

Shirly Pinto, Ph.D., CVD – Atherosclerosis Team Lead, Merck Research Laboratories

4:15 Sponsored Presentations (Opportunities Available)

4:45 Beneficial and Adverse Effects of Glucokinase Activators on Glucose Metabolism in Rat Liver Cells

Gabriel Baverel, Ph.D., CEO and CSO, Metabolomics, Metabolys, Inc.

Using a metabolic flux approach, we show the potential beneficial and adverse effects of three gluco-kinase activator drug candidates for type2 diabetes. We report the gluco-kinase activators’ effects on glucose utilization and production, glycogen synthesis and degradation, lactic acid and triglyceride accumulation and on the citric acid cycle during glucose metabolism in rat liver cells. Our work illustrates the advantage of metabolic flux analysis for predicting early during the drug development process, both the efficacy and safety of very small amounts of antidiabetic drug candidates.

5:15 Connecting Mitochondrial Dysfunction and Diabetes

James Dykens, CEO, Eyecyte Therapeutics

Mitochondrial dysfunction contributes via bioenergetic and oxidative mechanisms to a host of degenerative and metabolic diseases, including diabetes. Mitochondrial Ca2+ dynamics alter insulin release, while production of free radicals yields dysregulation of glycolysis. Importantly, xenobiotic therapies for diabetes, e.g., biguanides and thiazolidinediones, directly undermine mitochondrial function thereby lowering blood glucose, albeit via an untoward mechanism. The latter results from cell culture conditions that model diabetes and anaerobic poise, not normal aerobic physiology.

5:45 End of Day

WEDNESDAY, OCTOBER 3

8:00 am Interactive Breakfast Breakout Discussion Groups

Targeting GPCRs

Moderator: Peter Cornelius, Ph.D., Director of Metabolic Diseases, SystaMedic Inc.

  • Screening strategies for discovery of novel GPCR agonists
  • GPCRs linked to incretin release
  • Targeting GPCRs in the periphery versus CNS

Cardiovascular Challenges

Moderator: Rebecca Taub, CEO, Madrigal Pharmaceuticals

  • Cardiovascular disease in diabetics—why the high incidence
  • History of anti-diabetic therapies effects on diabetic CV disease
  • Update on regulatory requirements to show CV safety with new diabetic therapies

Better Diabetes Models and Markers

Moderator: Jerome J. Schentag, PharmD, Professor of Pharmaceutical Sciences, University at Buffalo

  • Are there diabetes biomarkers coming forward that offer sufficient advantages to replace our current reliance on glucose and HBA1c?
  • What models and biomarkers are best suited to re-cast our perspective on diabetes as a cardiovascular event with MACE consequences?
  • Should we consider biomarkers of Type 1 diabetes to be different than for Type 2 diabetes from the perspective of CV events and metabolic syndrome?


TARGETING MEMBRANE PROTEINS FOR TYPE2 DIABETES

9:05 Chairperson’s Remarks

Peter Cornelius, Ph.D., Director of Metabolic Diseases, SystaMedic Inc.

9:10 FEATURED PRESENTATION

Discovery of Ertugliflozin: An Anti-Diabetic Agent from a New Class of SGLT2 Inhibitors

Vincent MascittiVincent Mascitti, Ph.D., Senior Director, Pfizer Global R&D

Inhibition of sodium-dependent glucose co-transporter 2 (SGLT2), located in the kidney, promotes reduction of plasma glucose concentration. The medicinal and synthetic organic chemistry rationale that led to the rapid identification of Ertugliflozin (PF-04971729), an anti-diabetic agent currently in development and belonging to a new class of SGLT2 inhibitors bearing a dioxa-bicyclo[3.2.1]octane bridged ketal motif, will be presented.

9:40 Targeting FGF21 for Type 2 Diabetes

Andrew C. Adams, Ph.D., Post-Doctoral Research Fellow, Diabetes Research, Lilly Research Laboratories

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Update on the Clinical Candidate ARRY-981: A GPR119 Agonist

Brad Fell, Senior Research Investigator, Medicinal Chemistry, Array BioPharma

GPR119 is a promising new target for the treatment of type 2 diabetes. Agonists of this GPCR, which promote insulin secretion from pancreatic ß-cells and GLP-1 release from enteroendocrine L-cells, provide a unique opportunity for a single drug to elicit insulin secretion via two distinct pathways. However, several GPR119 agonists have recently demonstrated poor clinical efficacy. We will discuss our novel GPR119 clinical candidate, ARRY-981, that has shown meaningful and durable glucose control in preclinical models of diabetes.

11:25 Inflammation, Obesity and Diabetes: Pre-Clinical Investigations of a CCR2 Antagonist

Dana Johnson, Ph.D., Senior Scientific Director, Drug Discovery, Janssen Pharmaceuticals, Johnson & Johnson

With the growing idea of insulin resistance due, in part, to low grade systemic inflammation, mechanistic investigations aimed at altering inflammatory tone have been undertaken by us as well as others. Recruitment of the macrophage and continued activity in the adipose tissue appears to drive insulin resistance, in part, via the secretion of Moncocyte Chemoattractant Protein 1 (MCP-1) and its cognate receptor C-C Chemokine Receptor-2 (CCR2). Our efforts in disrupting the macrophage recruitment via the use of CCR2 antagonists will be presented.

11:55 Monoclonal Antibody Antagonists of the Glucagon Receptor as Therapeutic Agents

Bernard B. Allan, Ph.D., Scientist, Department of Molecular Biology, Genentech, Inc.

Excess glucagon signaling plays a key role in the development of hyperglycemia in type 1 and type 2 diabetic patients. We have generated potent anti-glucagon receptor antagonist antibodies and will present the mechanisms underlying their anti-diabetic activities in pre-clinical models, including their direct effects on hepatic glucose metabolism and indirect effects on beta-cell mass.

12:25 pm Sponsored Presentation (Opportunity Available)

12:40 Luncheon Workshop (Sponsorship Opportunity Available) or Lunch on Your Own


NEW THERAPEUTIC APPROACHES

1:55 Chairperson’s Remarks

Jesper Gromada, Ph.D., Executive Director, Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research

2:00 XMetA, an Allosteric Agonist Antibody to the Insulin Receptor that Selectively Activates Insulin Receptor Metabolic Signaling and Restores Glycemic Control in Mouse Models of Diabetes

John Corbin, Ph.D., Associate Director, Molecular Interactions and Biophysics, Preclinical Research, XOMA

The XMetA antibody represents novel drug class for the treatment of diabetes. XMetA has unique properties including selective partial agonism of insulin receptor metabolic signaling resulting in improvements in the disease state of both hyperinsulinemic insulin resistant and insulinopenic diabetic animals. The in vitro and in vivo data to be presented for XMetA will provide a clear demonstration of how allosteric modulation of the insulin receptor with a monoclonal antibody can translate to improvements in disease.

2:30 Phenotype-Driven Approaches towards Novel Beta-Cell Proliferative and Protective Therapies

Bryan Laffitte, Ph.D., Associate Director, Genomics Institute of the Novartis Research Foundation

Type 1 and type 2 diabetes are characterized by a loss of beta cell mass. However, therapeutic options aimed at preservation or restoration of endogenous beta cell mass, are not currently available. We used phenotypic screening approaches for both small molecule and biologic agents to identify regulators of beta cell survival and beta cell proliferation. We report on several series of small molecules that induce beta cell proliferation and/or protect beta cells from various forms of stress and have potential as therapeutic options for both type 1 and type 2 diabetes.

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

3:40 Gastric Bypass in Mice as a Model for Target Identification

Vincent Aguirre, M.D., Ph.D., Assistant Professor, Internal Medicine, University of Texas Southwestern Medical Center

We will discuss a mouse model of gastric bypass, which recapitulates effects of this procedure on body weight, body composition, glucose homeostasis, and stool energy observed in humans. The reproducibility of this model allows high-resolution comparison of effects of gastric bypass across genetic models using advanced methodologies, such as MRS metabolic flux, proteo metabolomics, and deep sequencing. As such, it enables targeted investigation of bypass-induced biological pathways and refined identification of novel pharmaceutical targets capable of mimicking beneficial effects of bariatric surgery.

4:10 Cell-Based Therapies to Treat Diabetes

Norma Kenyon, Ph.D., Professor of Surgery, Microbiology and Immunology and Biomedical Engineering; Executive Director of the Wallace H. Coulter Center for Translational Research; School of Medicine, University of Miami

This presentation will focus on the role of stem cell-based therapies to treat diabetes, highlighting the therapeutic potential of mesenchymal stem cells in diabetes. Our research group’s focus is on ways to transplant islet cells without the need for anti-rejection drugs, including the incorporation of stem cells into transplant protocols.

4:40 Discovery of Lorcaserin: A Selective 5-HT2C Agonist for Weight Management

Graeme Semple, Ph.D., Vice President, Discovery Chemistry, Arena Pharmaceuticals, Inc.

Compelling evidence suggests that drugs which activate the 5-HT2C receptor cause weight loss and thus have potential for use as weight management agents. Because serotonin elicits a number of biological responses through modulation of other 5HTrelated proteins, selectivity was a critical challenge particularly with respect to the closely related 5-HT2A and 5-HT2B receptors. This presentation outlines some of events, challenges and achievements that led to the discovery and development of lorcaserin.

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