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114. The apéritif effect: alcohol's effects on the brain's response to food aromas in women

Author

Eiler, William J.A., Džemidžić, Mario, Case, K. Rose, Soeurt, Christina M., Armstrong, Cheryl L.H., Mattes, Richard D., O'Connor, Sean J., Harezlak, Jaroslaw, Acton, Anthony J., Considine, Robert V., and Kareken, David A.

Subjects
Leptin, Adult, Hypothalamus, Article, Young Adult, Reward, Functional Magnetic Resonance Imaging, Humans, Obesity, Apéritif, Brain Mapping, Ethanol, digestive, oral, and skin physiology, food and beverages, Brain, Feeding Behavior, Olfaction, Magnetic Resonance Imaging, Ghrelin, Smell, Food, Reward Value, Odorants, Female, Cues, Alcohol
Abstract

Objective Consuming alcohol prior to a meal (an apéritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either roast beef or Italian meat sauce following pharmacokinetically controlled intravenous infusion of alcohol. Methods BOLD activation to food aromas in non-obese women (n=35) was evaluated once during intravenous infusion of 6% v/v EtOH, clamped at a steady-state breath alcohol concentration of 50 mg/dL, and once during infusion of saline using matching pump rates. Ad libitum intake of roast beef with noodles or Italian meat sauce with pasta following imaging was recorded. Results BOLD activation to food relative to non-food odors in the hypothalamic area was increased during alcohol pre-load when compared to saline. Food consumption was significantly greater, and levels of ghrelin were reduced, following alcohol. Conclusions An alcohol pre-load increased food consumption and potentiated differences between food and non-food BOLD responses in the region of the hypothalamus. The hypothalamus may mediate the interplay of alcohol and responses to food cues, thus playing a role in the apéritif phenomenon.

Published
2015

118. Leptin is related to body fat content in male distance runners

Author

Hickey, Matthew S., Considine, Robert V., Israel, Richard G., Mahar, Tyson L., McCammon, Michael R., Tyndall, Gilian L., Houmard, Joseph A., and Caro, Jose F.

Subjects
Leptin -- Physiological aspects, Exercise -- Physiological aspects, Runners (Sports) -- Physiological aspects, Adipose tissues -- Physiological aspects, Biological sciences
Abstract

Several studies have shown that leptin is correlated with body fat. In an analysis of serum leptin levels measured in male distance runners following a 20-mile treadmill run, there were no significant changes in leptin levels before and after the exercise, showing that acute exercise has no effect on serum leptin levels. However, serum leptin was closely correlated with body fat. This suggests that leptin levels is a good indicator of body fat.

Published
1996

123. Metabolic improvements following Roux-en-Y surgery assessed by solid meal test in subjects with short duration type 2 diabetes

Author

Shankar, Sudha S., primary, Mixson, Lori A., additional, Chakravarthy, Manu, additional, Chisholm, Robin, additional, Acton, Anthony J., additional, Jones, RoseMarie, additional, Mattar, Samer G., additional, Miller, Deborah L., additional, Petry, Lea, additional, Beals, Chan R., additional, Stoch, S. Aubrey, additional, Kelley, David E., additional, and Considine, Robert V., additional

Published
2017
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124. Profound defects in β-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP)

Author

Patel, Yash R., Kirkman, M. S., Hannon, Tamara S., Considine, Robert V., and Mather, Kieren J.

Abstract

BACKGROUND: Few studies have measured the ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes. The Early Diabetes Intervention Programme (ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycaemia in screen-detected type 2 diabetes. In the Early Diabetes Intervention Programme, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycaemia over a 5-year period was not greater than that of placebo. However, there was an early glucose-lowering effect of the trial. The objective of the current secondary analysis was to describe β-cell function changes in response to glucose lowering. METHODS: Participants were overweight adult subjects with screen-detected type 2 diabetes. β-cell function was measured using hyperglycaemic clamps and oral glucose tolerance testing. The primary outcome was the change in β-cell function from baseline to year 1, the time point where the maximal glucose-lowering effect was seen. RESULTS: At baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, fasting plasma glucose (PG) and 2-h PG, there was no clinically significant improvement in the first-phase insulin response. Late-phase insulin responses declined despite beneficial glycaemic effects of interventions. CONCLUSIONS: Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of β-cell function.

Published
2014
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125. Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes.

Author

Sims, Emily K., Bahnson, Henry T., Nyalwidhe, Julius, Haataja, Leena, Davis, Asa K., Speake, Cate, DiMeglio, Linda A., Blum, Janice, Morris, Margaret A., Mirmira, Raghavendra G.., Nadler, Jerry, Mastracci, Teresa L., Marcovina, Santica, Wei-Jun Qian, Lian Yi, Swensen, Adam C., Yip-Schneider, Michele, Schmidt, C. Max, Considine, Robert V., and Arvan, Peter

Abstract

Objective: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin.Research Design and Methods: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years.Results: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide.Conclusions: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide. [ABSTRACT FROM AUTHOR]

Published
2019
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127. Hexosamines Stimulate Leptin Production in Transgenic Mice

Author

CONSIDINE, ROBERT V., COOKSEY, ROBERT C., and MCCLAIN, DON

Subjects
Diabetes -- Research, Health
Abstract

Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel [...]

Published
2000

128. Hexosamines Regulate Leptin Production through Transcriptional Mechanisms

Author

ZHANG, PEILI, WILLIAMS, LLOYD B., and CONSIDINE, ROBERT V.

Subjects
Hexosamines -- Physiological aspects, Leptin -- Physiological aspects, Glucose metabolism -- Physiological aspects, Health
Abstract

We have previously demonstrated that hexosamines regulate leptin production in human subcutaneous adipocytes. This study was undertaken to examine the regulation of ob gene transcription by hexosamines. 3T3-L1 cells were [...]

Published
2000

129. TNF[Alpha] Inhibits Leptin Production in Human Subcutaneous and Omental Adipocytes

Author

FAWCETT, RACHAEL L, WAECHTER, ANGELA S, WILLIAMS, LLOYD B, JONES, ROSEMARIE, INMAN, MARGARET, HUSE, JOHN, and CONSIDINE, ROBERT V

Subjects
Diabetes -- Research, Health
Abstract

The ability of cytokines to influence leptin release has been controversial. This study was undertaken to examine the regulation of leptin production from human adipocytes by tumor necrosis factor [Alpha]. [...]

Published
1999

130. Hexosamines Regulate Leptin Production in Human Subcutaneous Adipocytes

Author

CONSIDINE, ROBERT V, COOKSEY, ROBERT C, WILLIAMS, LLOYD B, ZHANG, PEILI, JONES, ROSEMARIE, INMAN, MARGARET, HUSE, JOHN, WHITFIELD, ROBERT M, and MCCLAIN, DONALD A

Subjects
Diabetes -- Research, Health
Abstract

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells 'sense' nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of [...]

Published
1999

131. Comparison of β-Cell Function Between Overweight/Obese Adults and Adolescents Across the Spectrum of Glycemia.

Author

Chen, Melinda E., Chandramouli, Aaditya G., Considine, Robert V., Hannon, Tamara S., and Mather, Kieren J.

Subjects
PATHOLOGY, TYPE 2 diabetes, B cells, GLUCOSE tolerance tests, C-peptide
Abstract

Objective: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance.Research Design and Methods: We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage.Results: In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1-2.4] × 10-4; adults, 5.0 [2.3-9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103-284] × 10-9/min adolescent vs. 106 [71-127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0-10.3] × 10-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7 [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630-3,913] × 10-9; dysglycemia, 2,703 [1,323-3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001).Conclusions: Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults. [ABSTRACT FROM AUTHOR]

Published
2018
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135. Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation

Author

Patel, Meghana N., primary, Bernard, William G., additional, Milev, Nikolay B., additional, Cawthorn, William P., additional, Figg, Nichola, additional, Hart, Dan, additional, Prieur, Xavier, additional, Virtue, Sam, additional, Hegyi, Krisztina, additional, Bonnafous, Stephanie, additional, Bailly-Maitre, Beatrice, additional, Chu, Yajing, additional, Griffin, Julian L., additional, Mallat, Ziad, additional, Considine, Robert V., additional, Tran, Albert, additional, Gual, Philippe, additional, Takeuchi, Osamu, additional, Akira, Shizuo, additional, Vidal-Puig, Antonio, additional, Bennett, Martin R., additional, and Sethi, Jaswinder K., additional

Published
2014
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140. Acute and Second-Meal Effects of Almond Form in Impaired Glucose Tolerant Adults: A Randomized Crossover Trial

Author

Mori, Alisa M, Considine, Robert V, Mattes, Richard D, Mori, Alisa M, Considine, Robert V, and Mattes, Richard D

Abstract

Background Nut consumption may reduce the risk of developing type 2 diabetes. The aim of the current study was to measure the acute and second-meal effects of morning almond consumption and determine the contribution of different nut fractions. Methods Fourteen impaired glucose tolerant (IGT) adults participated in a randomized, 5-arm, crossover design study where whole almonds (WA), almond butter (AB), defatted almond flour (AF), almond oil (AO) or no almonds (vehicle - V) were incorporated into a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations of blood glucose, insulin, non-esterified free fatty acids (NEFA), glucagon-like peptide-1 (GLP-1) and appetitive sensations were assessed after treatment breakfasts and a standard lunch. Results WA significantly attenuated second-meal and daylong blood glucose incremental area under the curve (AUCI) and provided the greatest daylong feeling of fullness. AB and AO decreased blood glucose AUCI in the morning period and daylong blood glucose AUCI was attenuated with AO. WA and AO elicited a greater second-meal insulin response, particularly in the early postprandial phase, and concurrently suppressed the second-meal NEFA response. GLP-1 concentrations did not vary significantly between treatments. Conclusions Inclusion of almonds in the breakfast meal decreased blood glucose concentrations and increased satiety both acutely and after a second-meal in adults with IGT. The lipid component of almonds is likely responsible for the immediate post-ingestive response, although it cannot explain the differential second-meal response to AB versus WA and AO.

Published
2011

146. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians

Author

de Courten, Barbora, Degawa-Yamauchi, Mikako, Considine, Robert V, Tataranni, P Antonio, Volarova de Courten, Barbora, de Courten, Barbora, Degawa-Yamauchi, Mikako, Considine, Robert V, Tataranni, P Antonio, and Volarova de Courten, Barbora

Abstract

Resistin is an adipokine with putative prodiabetogenic properties. Like other hormones secreted by adipose tissue, resistin is being investigated as a possible etiologic link between excessive adiposity and insulin resistance. Although there is growing evidence that circulating levels of this adipokine are proportional to the degree of adiposity, an effect on insulin resistance in humans remains unproven. To evaluate the relations among resistin, obesity, and insulin resistance, we measured fasting serum resistin levels in 113 nondiabetic (75-g oral glucose tolerance test) Pima Indians (ages 29 +/- 7 years, body fat 31 +/- 8%, resistin 3.7 +/- 1.1 ng/ml [means +/- SD]), who were characterized for body composition (assessed by hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M; assessed by hyperinsulinemic clamp), basal hepatic glucose output (BHGO) and hepatic glucose output during low-dosage insulin infusion of a hyperinsulinemic clamp (HGO; a measure of hepatic insulin resistance), and acute insulin secretory response (AIR; assessed by 25-g intravenous glucose tolerance test). Follow-up measurements of M, BHGO, HGO, and AIR were available for 34 subjects who had normal glucose tolerance at baseline and remained nondiabetic at follow-up. The average time to follow-up was 4.5 +/- 2.7 years. In cross-sectional analyses, serum resistin levels were positively associated with percent body fat (r = 0.37, P = 0.0001) and 2-h glucose (r = 0.19, P = 0.04), respectively. Serum resistin levels were not associated with fasting glucose and insulin levels, M, BHGO, HGO, or AIR (r = 0.17, 0.12, -0.13, -0.06, -0.03, and -0.04, respectively; all P > 0.05). After adjusting for percent body fat, there was no association between serum resistin levels and 2-h glucose (r = 0.06, P = 0.6). In prospective analyses, high serum resistin levels at baseline were not associated with a decline in M (r = -0.1, P > 0.5). Resistin levels were, however

Published
2004

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