Human and porcine insulins are equally effective in the regulation of glucose kinetics of diabetic patients during exercise

1984 ◽  
Vol 107 (4) ◽  
pp. 500-505 ◽  
Author(s):  
Veikko A. Koivisto ◽  
Risto Pelkonen ◽  
Esko A. Nikkilä ◽  
Lise G. Heding

Abstract. The rate of hepatic glucose production (Ra) and peripheral utilization (Rd) was determined in 8 insulin-dependent diabetic subjects in basal state and during 40 min cycle ergometric exercise. The patients were treated with continuous sc infusion of either semisynthetic human or porcine (Actrapid®) insulin. Basal rate of glucose production was comparable during human (2.29 ± 0.19 mg/kg/min) and porcine (2.18 ± 0.12 mg/kg/min) insulin therapy. In response to exercise, Ra rose 30 to 40% (P < 0.05), to 2.85 ± 0.35 vs 3.18 ± 0.42 mg/kg/min, similarly during both studies. The peak rise in Rd (to 3.20 ± 0.32 during human vs 3.78 ± 0.44 mg/kg/min during porcine insulin) was comparable in both groups and not significantly different from the rise in Ra. Consequently, blood glucose levels remained unchanged. During the exercise tests, the metabolic conditions were stable and comparable in both studies, as indicated by similar levels of blood glucose, plasma free insulin HbA1, serum lipids and insulin binding to erythrocytes. In conclusion, semisynthetic human insulin is equally effective as porcine insulin in regulating glucose kinetics in the basal state and during exercise.

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 463-469 ◽  
Author(s):  
Hitoshi Ando ◽  
Kentaro Ushijima ◽  
Shigeki Shimba ◽  
Akio Fujimura

Abstract Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production–related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.


Metabolism ◽  
1996 ◽  
Vol 45 (10) ◽  
pp. 1196-1202 ◽  
Author(s):  
A. Riccio ◽  
G. Lisato ◽  
S. Vigili de Kreutzenberg ◽  
S. Marchetto ◽  
M. Turrin ◽  
...  

1998 ◽  
Vol 84 (4) ◽  
pp. 1413-1417 ◽  
Author(s):  
Kirsten Howlett ◽  
Damien Angus ◽  
Joseph Proietto ◽  
Mark Hargreaves

This study examined the effect of increased blood glucose availability on glucose kinetics during exercise. Five trained men cycled for 40 min at 77 ± 1% peak oxygen uptake on two occasions. During the second trial (Glu), glucose was infused at a rate equal to the average hepatic glucose production (HGP) measured during exercise in the control trial (Con). Glucose kinetics were measured by a primed continuous infusion ofd-[3-3H]glucose. Plasma glucose increased during exercise in both trials and was significantly higher in Glu. HGP was similar at rest (Con, 11.4 ± 1.2; Glu, 10.6 ± 0.6 μmol ⋅ kg−1 ⋅ min−1). After 40 min of exercise, HGP reached a peak of 40.2 ± 5.5 μmol ⋅ kg−1 ⋅ min−1in Con; however, in Glu, there was complete inhibition of the increase in HGP during exercise that never rose above the preexercise level. The rate of glucose disappearance was greater ( P < 0.05) during the last 15 min of exercise in Glu. These results indicate that an increase in glucose availability inhibits the rise in HGP during exercise, suggesting that metabolic feedback signals can override feed-forward activation of HGP during strenuous exercise.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gireesh Dayma

Abstract Background and Aims The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Method Adult male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 ?g/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. Results After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Conclusion Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.


1983 ◽  
Vol 245 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
E. W. Kraegen ◽  
D. E. James ◽  
S. P. Bennett ◽  
D. J. Chisholm

Our aim was to develop the glucose clamp (GC) technique in the conscious rat for assessment of in vivo insulin sensitivity. A 2-h euglycemic GC could be performed in chronically cannulated rats using 625 microliter blood. Overnight-fasted rats were infused with porcine insulin (1.67 mU . kg-1 . h-1). Insulin levels of 41 +/- 2 (SE) mU/liter were produced in rats aged 91 +/- 4 days with a 60- to 120-min glucose infusion rate (GIR60-120) of 10.6 +/- 0.6 mg . kg-1 . min-1 (n = 9) during euglycemia. GIR60-120 was significantly (P less than 0.025) reduced in rats aged greater than 130 days (mean, 169 +/- 16 days) to 7.7 +/- 1.2 mg . kg-1 . min-1 (n = 7). Metabolic clearance rate of porcine insulin (46 +/- 3 ml . kg-1 . min-1) and GIR60-120 compared with plateau plasma insulin levels are higher than values reported in humans. The latter may be due to suppression of a higher basal hepatic glucose production or increased potency of porcine compared with native insulin. We conclude that the GC can be accomplished in the rat. When combined with tracer administration and subsequent killing, it should provide a quantitative in vivo measurement of insulin sensitivity in individual tissues.


2001 ◽  
Vol 90 (2) ◽  
pp. 601-605 ◽  
Author(s):  
Damien J. Angus ◽  
Mark A. Febbraio ◽  
David Lasini ◽  
Mark Hargreaves

Six endurance-trained men [peak oxygen uptake (V˙o 2) = 4.58 ± 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 ± 2% peak V˙o 2 in an environmental chamber maintained at 35°C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 μCi [3-3H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (Ra) in Con trial] and glucose disappearance (Rd), were measured using a primed, continuous infusion of [6,6-2H]glucose, corrected for gut-derived glucose (gut Ra) in the CHO trial. No differences in heart rate, V˙o 2, respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased ( P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut Ra after 30 and 50 min (16 ± 5 μmol · kg−1 · min−1) was higher ( P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose Rd was higher ( P < 0.05) in the CHO trial after 30 and 50 min (48.0 ± 6.3 vs 34.6 ± 3.8 μmol · kg−1 · min−1, CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of ∼1.0 g/min, increases glucose Rd but does not blunt the rise in HGP during exercise in the heat.


1982 ◽  
Vol 62 (2) ◽  
pp. 131-136 ◽  
Author(s):  
I. Lager ◽  
U. Smith

1. Previous studies have shown that non-selective β-adrenoceptor blockade attenuates the blood glucose recovery rate after hypoglycaemia in type I diabetes. Apart from possible effects on hepatic glycogenolysis propranolol also inhibits the release of the important gluconeogenic substrates lactate and glycerol. 2. To determine whether the effect of non-selective β-adrenoceptor blockade on glucose recovery could be associated with diminished availability of gluconeogenic substrates, lactate and glycerol were infused during hypoglycaemia in four insulin-dependent diabetic patients. Comparisons were made of the blood glucose recovery on placebo, propranolol and propranolol combined with the infusion. 3. The blood glucose recovery rate after hypoglycaemia was less on propranolol than with placebo but was significantly improved and not different from placebo when propranolol treatment was combined with lactate and glycerol infusions. Thus, at least for type I diabetic patients, in whom gluconeogenesis is proportionally greater than in healthy subjects, non-selective β-adrenoceptor blockade attenuates the glucose recovery rate from hypoglycaemia mainly by reducing the availability of gluconeogenic substrates.


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