Karen L. Teff - US grants
Affiliations: | Monell Chemical Senses Center, Philadelphia, PA, United States |
Area:
Human Diabetes and ObesityWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Karen L. Teff is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
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| 1996 — 1998 | Teff, Karen L | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Sensory Stimuli, Neural Activity and Glucoregulation @ Monell Chemical Senses Center |
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| 2000 — 2003 | Teff, Karen L | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Vagal Control of Insulin Release in Humans @ Monell Chemical Senses Center |
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| 2008 — 2009 | Teff, Karen L | R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
The Cholinergic Anti-Inflammatory Pathway in Human Obesity and Insulin Resistance @ Monell Chemical Senses Center [unreadable] DESCRIPTION (provided by applicant): In light of the increasing prevalence of obesity in our society, elucidation of novel regulatory pathways that could potentially limit the pathophysiological consequences of obesity is of great importance. Elevated inflammatory cytokines are thought to contribute to insulin resistance and the development of chronic metabolic diseases such as type II diabetes, atherosclerosis and cardiovascular disease in obese individuals (1-3). In obese, insulin resistant subjects, macrophage activation increases release of inflammatory cytokines and there is increased macrophage accumulation in adipose tissue (4-7). Exciting new findings demonstrate a link between the central nervous system and regulation of cytokine release from macrophages. Termed the 'cholinergic anti-inflammatory pathway', the data suggest that the release of acetylcholine from vagal efferent fibers inhibits macrophage activation and the subsequent release of inflammatory cytokines (8-12). My laboratory is one of very few to study the role of the vagus nerve in the regulation of glucose homeostasis in humans (13-15). This proposal will apply our knowledge and expertise of vagal physiology to explore for the first time, the role of the nicotinic acetylcholine receptor in vagally mediated inflammatory responses in human obesity. We will test the hypothesis that pharmacological activation of the Nicotinic Acetylcholine Receptor (NAcR) by nicotine will decrease the elevated circulating inflammatory cytokines in obese, insulin resistant humans. The aim of the project is to determine if activation of nicotinic acetylcholine receptors by nicotine administration decreases markers of inflammation. The exploratory aim will evaluate the effect of nicotine administration on insulin sensitivity and sympathetic nervous system activity (SNS) obese insulin resistant subjects. We will use a within subject, crossover design and administer either transdermal nicotine, a known agonist of the nicotinic acetylcholine receptor 1-7 subunit or co-administer transdermal nicotine and the nicotinic acetylcholine receptor antagonist, mecamylamine. During both conditions, we will measure markers of inflammation: IL-6, TNF-1, TNF-1 receptor 2, resistin and the anti- inflammatory marker IL-10. In addition, we will measure insulin sensitivity using the frequently sampled intravenous glucose tolerance test and SNS activity with heart rate variability and urinary catecholamines. This translational study will investigate a previously unexplored mechanism which may contribute to the inflammatory state associated with human insulin resistance. Findings from this study will provide a scientific basis for future translational studies and elucidate a potential therapeutic target for pharmacological intervention. [unreadable] PUBLIC HEALTH RELEVANCE: Elevated levels of cytokines, proteins associated with inflammation, may be responsible for some of the adverse consequences of metabolic diseases such as obesity, type 2 diabetes, cardiovascular disease and atherosclerosis. This study will investigate a novel regulatory pathway regulating cytokine levels in humans. Positive findings would support future investigations for the development of a new therapeutic target to lower cytokine levels in obese individuals. [unreadable] [unreadable] [unreadable] [unreadable] |
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| 2009 — 2012 | Teff, Karen L | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Atypical Antipsychotics: Effects On Hepatic Glucose and Lipid Metabolism in Human @ Monell Chemical Senses Center DESCRIPTION (provided by applicant): The use of the atypical antipsychotic (AAPs) medications is associated with a dramatic increase in the incidence of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in the schizophrenic population. AAPs induce tremendous weight gain in patients and to date, metabolic consequences are thought to be secondary to increased body adiposity. However, preliminary data from our laboratory demonstrate direct effects on the pancreatic b-cell and the liver independent of weight gain or psychiatric disease. We have found increased endogenous glucose production, post-prandial hyperinsulinemia and hypertriglyceridemia as well as decreased insulin sensitivity after only 9 days of olanzapine administration to healthy control subjects. In the proposed inpatient studies, we will expand these findings and examine the effects of olanzapine and aripiprazole compared to placebo on hepatic glucose and lipid metabolism in normal weight control subjects. The overall hypothesis is that olanzapine blocks muscarinic inhibition of endogenous glucose production, resulting in increased EGP and hyperinsulinemia which in turn promote lipogenesis. In contrast, aripiprazole is expected to exhibit limited effects on lipid and glucose metabolism. SPA1: Determine if the olanzapine-induced increase in endogenous glucose production is due to decreased hepatic insulin sensitivity. In Study 1, normal weight control subjects will be randomized to one of three experimental conditions; olanzapine, aripiprazole or placebo. Subjects will undergo a euglycemic, hyperinsulinemic clamp with infusion of 6,6-[2H2]-glucose to determine endogenous glucose production. We will compare the magnitude of suppression of endogenous glucose production by hyperinsulinemia prior to and following drug administration. SPA2: Determine if olanzapine prevents muscarinic suppression of endogenous glucose production. In Study 2, after treatment randomization as described above, subjects will undergo a pancreatic islet clamp with a stable isotope infusion. We will determine the effect of the muscarinic agonist bethanechol on EGP prior to and following AAP administration. SPA3: Determine if olanzapine induces an increase in hepatic de novo lipogenesis and VLDL- apoB100 production. In Study 3, following treatment randomization, subjects will undergo an 17-h infusion of [1-13C] labeled acetate and 15-h infusion of [5,5,5,-2H3] labeled leucine to determine hepatic de novo lipogenesis and VLDL apobB100 production prior to and following administration of the AAPs or placebo. Findings from these studies will explain why olanzapine and potentially other AAPs are associated with metabolic disease, help direct future mechanistic studies in clinical populations and provide insight on the role of the nervous system in glucose homeostasis and the etiology of T2DM. PUBLIC HEALTH RELEVANCE: The atypical antipsychotics (AAPs) used for the treatment of schizophrenia and bipolar disease are associated with tremendous weight gain and increased incidence of diabetes. These drugs may directly impair functioning of the pancreas and the liver but investigators have not been able to differentiate treatment-emergent effects from disease and weight gain. To separate drug effects on tissue function from weight gain or disease, we will investigate the effects of two AAPs, olanzapine and aripiprazole on glucose and liver metabolism in healthy control subjects. Findings from these studies will have important clinical relevance to the treatment of schizophrenia. |
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| 2011 — 2012 | Teff, Karen L | R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Sweet Taste Receptors and Glucose Metabolism in Healthy and T2dm Humans @ Monell Chemical Senses Center DESCRIPTION (provided by applicant): The recent identification of taste-receptor signaling elements in the gastrointestinal tract has fueled tremendous excitement with regards to the potential role of the taste system in nutrient sensing and nutrient metabolism. The G-protein coupled receptors, T1R2 and T1R3 which form the sweet taste receptor (STR) and gustducin, the G protein involved in taste signal transduction are all expressed in the small intestine of humans and other animals. Although the functional significance of these receptors in humans has yet to be demonstrated, recent animal model studies provide intriguing indications. Stimulation of the STR upregulates the intestinal sodium-glucose transporter (SGLT1), thereby, promoting glucose absorption from the intestinal lumen. In addition, because the taste signaling elements are co-expressed in the intestinal L-cells which secrete the hormone, glucagon-like peptide (GLP); during food ingestion, stimulation of the STR also elicits the release of GLP. Blockade of the STR with the inhibitor lactisole or genetic knock out of gustducin or T1R3 inhibits upregulation of SGLT1 and the GLP response to glucose. These data provide evidence for a role of the STR in regulating glucose absorption and intestinal hormone release. The possibility that the STR could increase or decrease GLP levels is of significant clinical interest as GLP plays a critical role in glucose homeostasis by stimulating insulin release, delaying gastric emptying and inhibiting hepatic glucose production. Patients with type 2 diabetes mellitus (T2DM) exhibit blunted GLP levels and enhancing GLP is the target of new diabetes therapeutics. In the proposed studies, we will bring our expertise in glucose metabolism and apply it to this exciting new area by using stable isotope methodologies to monitor post-prandial hormonal release as well as endogenous glucose production (EGP),the rate of appearance of ingested glucose and glucose disposal. To date, the effect of the STR on these indices of glucose metabolism have not been examined in humans. We are proposing to investigate the effects of stimulating (Specific Aim 1) and inhibiting (Specific Aim 2) the sweet taste receptor on GLP and post-prandial hormone release as well as indices of glucose metabolism in healthy subjects and patients with Type 2 diabetes mellitus (T2DM). Findings from the proposed studies will have important clinical implications with respect to the impact of dietary sugars and non- nutritive sweeteners on glucose homeostasis and the etiology of T2DM. Our overall hypothesis is that in healthy subjects, the STR receptor is involved in the regulation of post-prandial glucose metabolism and GLP levels but in T2DM, the STR receptor is unresponsive to activation or inhibition |
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