1085-P: Defining the Role of Insulin Clearance in Dysglycemia: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1085-P
Author(s):  
ALEXIS WOOD ◽  
ELIZABETH T. JENSEN ◽  
GAUTAM RAMESH ◽  
ZORAYR ARZUMANYAN ◽  
KELVIN LAM ◽  
...  
Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 420
Author(s):  
Alexis C. Wood ◽  
Elizabeth T. Jensen ◽  
Alain G. Bertoni ◽  
Gautam Ramesh ◽  
Stephen S. Rich ◽  
...  

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (prediabetes or newly diagnosed diabetes). In separate models, reduced insulin sensitivity, reduced disposition index, and reduced insulin clearance were associated with dysglycemia. In a joint model, only insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with insulin sensitivity, disposition index, or three insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.


Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.


Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5157-5164 ◽  
Author(s):  
Thomas A. Bowman ◽  
Sadeesh K. Ramakrishnan ◽  
Meenakshi Kaw ◽  
Sang Jun Lee ◽  
Payal R. Patel ◽  
...  

Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2–3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.


2018 ◽  
Vol Volume 13 ◽  
pp. 1059-1079 ◽  
Author(s):  
Irhan Abu Hashim ◽  
Noha Abo El-Magd ◽  
Ahmed El-Sheakh ◽  
Mohammed Hamed ◽  
Abd El-Gawad Abd El-Gawad

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 577
Author(s):  
Abdulaziz Alblwi ◽  
Dena Al-Thani ◽  
John McAlaney ◽  
Raian Ali

Procrastination refers to the voluntary avoidance or postponement of action that needs to be taken, that results in negative consequences such as low academic performance, anxiety, and low self-esteem. Previous work has demonstrated the role of social networking site (SNS) design in users’ procrastination and revealed several types of procrastination on SNS. In this work, we propose a method to combat procrastination on SNS (D-Crastinate). We present the theories and approaches that informed the design of D-Crastinate method and its stages. The method is meant to help users to identify the type of procrastination they experience and the SNS features that contribute to that procrastination. Then, based on the results of this phase, a set of customised countermeasures are suggested for each user with guidelines on how to apply them. To evaluate our D-Crastinate method, we utilised a mixed-method approach that included a focus group, diary study and survey. We evaluate the method in terms of its clarity, coverage, efficiency, acceptance and whether it helps to increase users’ consciousness and management of their own procrastination. The evaluation study involved participants who self-declared that they frequently procrastinate on SNS. The results showed a positive impact of D-Crastinate in increasing participants’ awareness and control over their procrastination and, hence, enhancing their digital wellbeing.


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