Marcello C Laurenti1, Chiara Dalla Man2, Ron T Varghese1, James C Andrews3, John G Jones4, Cristina Barosa4, Robert A Rizza1, Aleksey Matveyenko1,5, Giuseppe De Nicolao6, Kent R Bailey7, Claudio Cobelli2, Adrian Vella1. 1. Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic, Rochester, MN, USA. 2. Department of Information Engineering, University of Padova, Padova, Italy. 3. Vascular and Interventional Radiology, Mayo Clinic, Rochester, MN, USA. 4. Center for Neurosciences, University of Coimbra, Coimbra, Portugal. 5. Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. 6. Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy. 7. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
OBJECTIVE: Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action. METHODS: We studied 29 nondiabetic subjects on two occasions. On 1 occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day, we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used approximate entropy to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies. RESULTS: In univariate analysis, basal insulin secretion (R2 = 0.16) and insulin pulse amplitude (R2 = 0.09) correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex, and weight, these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis) or to stimulate glucose disappearance. CONCLUSIONS: Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in nondiabetic humans.
OBJECTIVE: Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action. METHODS: We studied 29 nondiabetic subjects on two occasions. On 1 occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day, we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used approximate entropy to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies. RESULTS: In univariate analysis, basal insulin secretion (R2 = 0.16) and insulin pulse amplitude (R2 = 0.09) correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex, and weight, these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis) or to stimulate glucose disappearance. CONCLUSIONS: Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in nondiabetic humans.
Authors: Marcello C Laurenti; Adrian Vella; Ron T Varghese; James C Andrews; Anu Sharma; Nana Esi Kittah; Robert A Rizza; Aleksey Matveyenko; Giuseppe De Nicolao; Claudio Cobelli; Chiara Dalla Man Journal: Am J Physiol Endocrinol Metab Date: 2019-02-26 Impact factor: 4.310
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Authors: Gerlies Bock; William C Schumann; Rita Basu; Shawn C Burgess; Zheng Yan; Visvanathan Chandramouli; Robert A Rizza; Bernard R Landau Journal: Diabetes Date: 2007-10-12 Impact factor: 9.461
Authors: M Laakso; J Zilinskaite; T Hansen; T Welløv Boesgaard; M Vänttinen; A Stancáková; P-A Jansson; F Pellmé; J J Holst; T Kuulasmaa; M L Hribal; G Sesti; N Stefan; A Fritsche; H Häring; O Pedersen; U Smith Journal: Diabetologia Date: 2007-12-14 Impact factor: 10.122
Authors: Marcello C Laurenti; Praveer Arora; Chiara Dalla Man; James C Andrews; Robert A Rizza; Aleksey Matveyenko; Kent R Bailey; Claudio Cobelli; Adrian Vella Journal: Physiol Rep Date: 2022-07