Relationship of substrate level to turnover rate in fasted adult and newborn dogs

1988 ◽  
Vol 254 (2) ◽  
pp. E137-E143 ◽  
Author(s):  
S. Hulman ◽  
R. Kliegman ◽  
J. Heng ◽  
E. Crouser

Glucose turnover, clearance and response to insulin were determined in fasted newborn and adult dogs. Fasting levels of glucose and insulin and rates of glucose turnover and clearance were not different between the two groups. Blood glucose correlated with basal glucose turnover in newborn pups but not in adult dogs. Glucose turnover was not related to fasting plasma insulin levels. Glucose clearance was an inverse function of blood glucose levels among newborn but not adult dogs. Glucose clearance and blood glucose levels were not related to insulin concentrations. In response to euglycemic hyperinsulinemia, glucose metabolism increased 4-fold among adults but only 1.7-fold in pups. Hyperglycemic hyperinsulinemia increased glucose metabolism in both groups but to a much greater extent in the pups. Euglycemic hyperinsulinemia increased the metabolic clearance rate of glucose 4.2-fold among adults but only 1.8-fold in newborn dogs. In response to hyperglycemic hyperinsulinemia glucose clearance rates were now similar. Despite euglycemic hyperinsulinemia, the newborn dog had an attenuated response to insulin, demonstrating lower rates of glucose metabolism and glucose clearance. The response to the hyperglycemic stimuli suggests that maximal glucose uptake was not achieved during hyperinsulinemia alone. This response supports the concept of glucose-mediated regulation of glucose disposal in newborn animals.

1990 ◽  
Vol 259 (3) ◽  
pp. E457 ◽  
Author(s):  
D A Young ◽  
R O Deems ◽  
R W Deacon ◽  
R H McIntosh ◽  
J E Foley

The effects of amylin on glucose metabolism and glycogenolysis were examined in vivo and in vitro. Eighteen-hour-fasted rats were infused with 5 nmol.kg-1.min-1 amylin and [3-3H]glucose for 120 min. Blood glucose levels increased an average of 45% during the infusion. Glucose turnover measurements indicated that the overall rate of glucose appearance (Ra) did not change, but the metabolic clearance rate of glucose was decreased by 42%. Samples of liver, gastrocnemius, and soleus muscles were freeze-clamped at the end of the infusion period and analyzed for glycogen and glucose 6-phosphate levels. Glycogen levels were decreased in all tissue samples, whereas glucose 6-phosphate was elevated in gastrocnemius and soleus muscles. Isolated soleus muscles were incubated in vitro with 200 microU/ml of insulin and 1, 10, or 100 nM amylin. Amylin treatment had no effect on 3-O-methyl-D-glucose transport; however, 2-deoxy-D-glucose uptake was inhibited by 33 or 48% at 10 or 100 nM amylin, respectively. Glycogen levels were also decreased after treatment with 10 and 100 nM amylin. Glucose 6-phosphate levels were not affected by amylin treatment in the presence of insulin but were increased nearly twofold in its absence. The data suggest that amylin stimulates glycogenolysis and inhibits glucose uptake both in vivo and in vitro and that the inhibition of glucose uptake is due to inhibition of glucose phosphorylation (i.e., hexokinase).


1983 ◽  
Vol 244 (5) ◽  
pp. E505-E512 ◽  
Author(s):  
G. A. Brooks ◽  
C. M. Donovan

Control and endurance-trained rats received continuous infusions via jugular catheters of [U-14C]- and [6-3H]glucose under one of three conditions: rest (Re), running at 13.4 m/min (easy exercise, EE), or running at 26.8 m/min (hard exercise, HE). Arterial blood was sampled from carotid catheters. Blood glucose levels were not different between groups at rest (3.88 +/- 0.19 mM) or EE (4.32 +/- 0.35 mM). During HE, trained animals maintained blood glucose better (3.41 +/- 0.34 mM) than did untrained animals (3.03 +/- 0.42 mM). Respiratory exchange ratio (R) increased from rest (0.79 +/- 0.05) to exercise and was significantly lower in trained than in untrained animals during HE (0.87 +/- 0.02 vs. 0.93 +/- 0.03). Glucose turnover (Rt) calculated from [3H]glucose was not different between groups at rest (46.2 +/- 2.7 mumol x kg-1 x min-1). Turnover increased during EE to 91.5 +/- 7.5 vs. 72 +/- 8.5 mumol x kg-1 x min-1 in untrained and trained animals, respectively. During HE, Rt rose to 95.0 +/- 12.6 in trained animals but fell to 78.7 +/- 9.9 mumol x kg-1 x min-1 in untrained animals. The percentage of glucose flux oxidized increased from rest (44.0 +/- 6.8%) to exercise and was significantly lower in trained (73.7 +/- 4.3%) than in untrained animals (95.1 +/- 3.8%) during HE. Metabolic clearance rate increased from 12.5 +/- 0.8 in Re to 29.4 +/- 6.0 ml x min-1 x kg-1 in HE but did not differ between groups. Training improved glucose homeostasis during HE by increasing the glucose flux and by reducing the fraction of the flux lost to oxidation.


2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Shiyi He ◽  
Ying Zhang

Objective Aerobic exercise training is important to prevent and cure chronic diseases such as diabetes, cardiovascular diseases and so on. Apelin has been identified as a novel myokine in recent years, and the exogenous supplementation of apelin can promote the glucose absorption, the biosynthesis of mitochondria and the oxidation of fatty acids in skeletal muscle. Intraperitoneal glucose (GTT) and insulin tolerance tests (ITT) are useful in vivo assays that provide approximations of glucose metabolism and homeostasis. The bigger area under the curve (AUC) confirmed the decreased glucose clearance, which is evaluated by GTT. However, the mechanism of apelin mediating glucose metabolism during aerobic exercise training is not clear. Our study was to investigate the differences of GTT and ITT after four weeks training between wild-type (WT) mice (C57BL/6J) and apelin Knockout (KO) mice. Methods Two-month-old WT and KO were divided into trained and control groups (n=8-10/group) respectively. There are four groups: WT control (WC), apelin KO control (KC), WT trained (WT), and apelin KO trained (KT). The trained groups were trained on treadmills for four weeks (six days per week and one hour per day). In order to maintain the exercise intensity, the speed is at 70%-75% VO2max with an incline of 5 degrees. The control groups were kept at a sedentary condition. after four weeks of interventions, glucose was measured at 0, 15, 30, 45, 60, 90, 120min following GTT. Glucose was also measured at 0, 30, 60, 90, 120min following ITT. Results  (1) blood glucose levels and AUC of the KC were significantly bigger than those of WC. ITT showed that KC also had slower insulin-stimulated glucose clearance compared with the WC. (2) Following 4-week training, KT had lower blood glucose levels and AUC of the KT was significantly smaller than those of KC. KT had faster insulin-stimulated glucose clearance compared with KC. Conclusions Without apelin, glucose tolerance and insulin tolerance in mice will decrease. And aerobic exercise training improves them in apelin deficiency mice.


2007 ◽  
Vol 34 (6) ◽  
pp. 916-925 ◽  
Author(s):  
M. L. Soto-Montenegro ◽  
J. J. Vaquero ◽  
C. Arango ◽  
G. Ricaurte ◽  
P. García-Barreno ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nasser M Rizk ◽  
Amina Saleh ◽  
Abdelrahman ElGamal ◽  
Dina Elsayegh ◽  
Isin Cakir ◽  
...  

Abstract The Expression of TBC1 Domain Family, member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane. Background: Obesity is commonly accompanied by impaired glucose homeostasis. Decreased glucose transport to the peripheral tissues, mainly skeletal muscle, leads to reduced total glucose disposal and hyperglycemia. TBC1D4 gene is involved in the trafficking of GLUT4 to the outer cell membrane in skeletal muscle. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound acting by reducing blood glucose levels through mechanisms not fully understood (1). The aim of this study is to investigate the effects SFN on TBC1D4 and GLUT4 gene expression in skeletal muscles of DIO mice, in order to elucidate the mechanism(s) through which SFN improves glucose homeostasis. Methodology: C57BL/6 mice (n=20) were fed with a high fat diet (60%) for 16 weeks to generate diet induced obese (DIO) mice with body weights between 45–50 gm. Thereafter, DIO mice received either SFN (5mg/kg BW) (n=10) or vehicle (n=10) as controls daily by intraperitoneal injections for four weeks. Glucose tolerance test (1g/kg BW, IP) and insulin sensitivity test (ITT) were conducted (1 IU insulin/ g BW, IP route) at the beginning and end of the third week of the injection. At the end of 4 weeks of the injection, samples of blood and skeletal muscles of both hindlimbs were collected. The expression levels of GLUT4 and TBC1D4 genes were analyzed by qRT-PCR. Blood was also used for glucose, adiponectin and insulin measurements. Results: SFN-treated DIO mice had significantly lower non-fasting blood glucose levels than vehicle-treated mice (194.16 ± 14.12 vs. 147.44 ± 20.31 mg/dL, vehicle vs. SFN, p value=0.0003). Furthermore, GTT results indicate that the blood glucose levels at 120 minutes after glucose infusion in was (199.83±34.53 mg/dl vs. 138.55±221.78 mg/dl) for vehicle vs. SFN with p=0.0011 respectively. ITT showed that SFN treatment did not enhance insulin sensitivity in DIO mice. Additionally, SFN treatment did not significantly change the expression of TBC1D4, and GLUT4 genes in skeletal muscles compared to vehicle treatment (p values >0.05). Furthermore, SFN treatment did not significantly affect the systemic insulin (1.84±0.74 vs 1.54±0.55 ng/ml, p=0.436), or adiponectin (11.96 ±2.29 vs 14.4±3.33 ug/ml, p=0.551) levels in SFN vs. vehicle-treated DIO mice, respectively. Conclusion: SFN treatment improves glucose disposal in DIO mice, which is not linked to the gene expression of GLUT4 and TBC1D4 and its mechanism of glucose disposal in skeletal muscles. Furthermore, SFN treatment did not improve insulin level, and the insulin sensitizer hormone adiponectin as potential players for enhancing insulin sensitivity. 1. Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sci Transl Med. 2017;9(394).


2014 ◽  
Vol 11 (1) ◽  
pp. 24-31
Author(s):  
I I Dedov ◽  
G A Melnichenko ◽  
E A Troshina ◽  
N V Mazurina ◽  
N A Ogneva ◽  
...  

We’ve studied a carbohydrate metabolism in morbidly obese (MO) patients and the patients after bariatric surgery. The patients of the 1st group had BMI40 (n=22) and no history of diabetes mellitus. Patients after biliopancreatic diversion (BPD) performed for MO were included in the 2nd group (n=23). The 3rd group was a control group of normal weight healthy subjects (n=22). Blood glucose levels, insulin, GLP-1, GIP and glucagon during the OGTT (with 75 g of glucose) at 0, 30, 60 and 120 minutes were measured in all patients. In MO group fasting glucose levels were the highest. Impaired glucose metabolism was revealed in 68.2% of patients (n=10). Impaired fasting glucose (IFG) was diagnosed in 4 cases (18.2%), impaired glucose tolerance (IGT) in 11 patients (50%). In the BPD postprandial blood glucose levels (120 min) were lower if compared to the other groups. In 4 individuals (17.4%) we found postprandial hypoglycemia (2.8 mmol/l). Patients of the MO group had the highest fasting insulin levels and HOMA-IR (p0.001). The maximum of insulin concentration was seen on minute 30 of the OGTT in the 2nd and 3rd groups, and it was significantly higher in the post-bariatric patients (p=0.026). In MO group the maximum of the plasma insulin levels were on the 60th minute and were still elevated after 120 minutes. Fasting and stimulated (on the 30th minute) levels of GLP-1 were significantly higher after BPD (р=0.037 and p=0.022 at 0 and 30 min, respectively). Morbidly obese patients had higher fasting and stimulated GIP. Fasting glucagon concentrations were similar in the surgical and control groups, while the people with MO had higher initial levels of glucagon (p=0.013) and it was not suppressed during the OGTT (p=0.076). Glucose intolerance and insulin resistance incidence was higher in MO patients. Hyperglucagonemia, increased GIP and decreased GLP-1 levels are observed in MO patients. Stimulated plasma insulin and GLP-1 concentrations were significantly increased in patients who underwent BPD, and may cause postprandial hypoglycemia.


Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 195-206 ◽  
Author(s):  
Hiroshi Tsuneki ◽  
Takashi Nagata ◽  
Mikio Fujita ◽  
Kanta Kon ◽  
Naizhen Wu ◽  
...  

Abstract Nicotine is known to affect the metabolism of glucose; however, the underlying mechanism remains unclear. Therefore, we here investigated whether nicotine promoted the central regulation of glucose metabolism, which is closely linked to the circadian system. The oral intake of nicotine in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat content, and serum levels of insulin. Nicotine administered at the active period appears to be responsible for the effect on blood glucose, because nighttime but not daytime injections of nicotine lowered blood glucose levels in db/db mice. The chronic oral treatment with nicotine suppressed the mRNA levels of glucose-6-phosphatase, the rate-limiting enzyme of gluconeogenesis, in the liver of db/db and wild-type control mice. In the pyruvate tolerance test to evaluate hepatic gluconeogenic activity, the oral nicotine treatment moderately suppressed glucose elevations in normal mice and mice lacking dopamine receptors, whereas this effect was abolished in orexin-deficient mice and hepatic parasympathectomized mice. Under high-fat diet conditions, the oral intake of nicotine lowered blood glucose levels at the daytime resting period in wild-type, but not orexin-deficient, mice. These results indicated that the chronic daily administration of nicotine suppressed hepatic gluconeogenesis via the hypothalamic orexin-parasympathetic nervous system. Thus, the results of the present study may provide an insight into novel chronotherapy for type 2 diabetes that targets the central cholinergic and orexinergic systems.


Author(s):  
Fumimaru Niwano ◽  
Naru Babaya ◽  
Yoshihisa Hiromine ◽  
Ippei Matsumoto ◽  
Keiko Kamei ◽  
...  

Abstract Context The rate of glucose metabolism changes drastically after partial pancreatectomy. Objective This work aims to analyze changes in patients’ glucose metabolism and endocrine and exocrine function before and after partial pancreatectomy relative to different resection types (Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy: KIP-MEP study). Methods A series of 278 consecutive patients with scheduled pancreatectomy were enrolled into our prospective study. Of them, 109 individuals without diabetes, who underwent partial pancreatectomy, were investigated. Data were compared between patients with pancreaticoduodenectomy (PD, n = 73) and those with distal pancreatectomy (DP, n = 36). Results Blood glucose levels during the 75-g oral glucose tolerance test (75gOGTT) significantly decreased after pancreatectomy in the PD group (area under the curve [AUC] –9.3%, P < .01), and significantly increased in the DP population (AUC + 16.8%, P < .01). Insulin secretion rate during the 75gOGTT and glucagon stimulation test significantly decreased after pancreatectomy both in the PD and DP groups (P < .001). Both groups showed similar homeostasis model assessment of insulin resistance (HOMA-IR) values after pancreatectomy. Decrease in exocrine function quality after pancreatectomy was more marked in association with PD than DP (P < .01). Multiple regression analysis indicated that resection type and preoperative HOMA-IR independently influenced glucose tolerance-related postoperative outcomes. Conclusions Blood glucose levels after the OGTT differed markedly between PD and DP populations. The observed differences between PD and DP suggest the importance of individualization in the management of metabolism and nutrition after partial pancreatectomy.


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