scholarly journals Hepatic Gluconeogenic Response to Single and Long-Term SGLT2 Inhibition in Lean/Obese Male Hepatic G6pc-Reporter Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (12) ◽  
pp. 2811-2824 ◽  
Author(s):  
Yuka Inaba ◽  
Emi Hashiuchi ◽  
Hitoshi Watanabe ◽  
Kumi Kimura ◽  
Makoto Sato ◽  
...  
Keyword(s):  
Single Dose ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Glucose Production ◽  
Obese Mice ◽  
Specific Expression ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Hepatic Insulin Signaling

Abstract Sodium-glucose cotransporter 2 inhibitor (SGLT2i) consistently reduces blood glucose levels in type 2 diabetes mellitus but increases hepatic gluconeogenic gene expression and glucose production, offsetting its glucose-lowering effect. This study aimed to elucidate the effect of SGLT2i on hepatic gluconeogenic response and its mechanism in both insulin-sensitive and insulin-resistant states. A hepatic mouse model was generated to show liver-specific expression of Gaussia luciferase (GLuc) driven by the gluconeogenic enzyme gene G6pc promoter. Hepatic gluconeogenic response was evaluated by measuring plasma GLuc activity. SGLT2i was given to lean and obese mice in single gavage administration or 4-week dietary administration with controlled feeding every 3 hours. In lean mice, single-dose SGLT2i increased plasma GLuc activity from 2 hours after administration, decreasing blood glucose and plasma insulin from 1 to 2 hours after administration. In obese mice, which had higher plasma GLuc activity than lean ones, SGLT2i did not further increase GLuc activity despite decreased blood glucose and plasma insulin. Hepatic Akt and GSK3β phosphorylation was attenuated by single-dose SGLT2i in lean mice in accordance with the plasma insulin decrease, but not in obese mice. Long-term SGLT2i administration, which increased plasma GLuc activity in lean mice, decreased it in obese mice from 3 weeks after initiation, with increased hepatic Akt and GSK3β phosphorylation. In conclusion, single SGLT2i administration increases hepatic gluconeogenic response in lean insulin-sensitive mice, but not in obese insulin-resistant mice. Long-term SGLT2i administration relieves obesity-induced upregulation of the hepatic gluconeogenic response by restoring impeded hepatic insulin signaling in obese insulin-resistant mice.

THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Hormone Levels ◽  
Glucose Levels ◽  
Ethynodiol Diacetate ◽  
Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

scholarly journals Preliminary phytochemical screening and evaluation of hypoglycemic properties of the root extract of Uveria chamae

2015 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Emordi Jonathan Emeka ◽  
Agbaje Esther Oluwatoyin ◽  
Oreagba Ibrahim Adekunle ◽  
Iribhogbe Osede Ignis
Keyword(s):  
Single Dose ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Phytochemical Screening ◽  
Glucose Levels ◽  
Blood Glucose Levels

<p>The purpose of this study is to evaluate the hypoglycaemic properties and preliminary phytochemical screening of <em>Uveria chamae</em>. The hypoglycaemic properties of <em>Uveria chamae</em> was assessed on normoglycaemic rat that received single dose of the extract at 250 and 500 mg/kg body weight and blood glucose levels estimated at 2, 4, and 6 hours (single dose study). The hypoglycaemic property of the extract was also evaluated in normoglycemic rats by oral glucose tolerance test. Phytochemical screening of the extract for the presence of secondary metabolites was performed with standard methods. The extract showed a significant (p&lt;0.05) reduction in blood glucose levels at 2h and 6h compared to control.  The oral glucose tolerance test  result also showed a significant decrease (p&lt;0.05) in blood glucose levels . The study showed that the extract, <em>Uveria chamae</em> has hypoglycaemic properties which may be accounted for by the presence of the phytochemicals.</p><p> </p>

scholarly journals Correlations between gingival crevicular blood glucose and capillary blood glucose: A preliminary report

2017 ◽  
Vol 9 (04) ◽  
pp. 260-263 ◽  
Author(s):  
Siluvai Sibyl ◽  
Darshana Bennadi ◽  
Nandita Kshetrimayum ◽  
Maurya Manjunath
Keyword(s):  
Blood Glucose ◽  
Oral Health ◽  
Analytical Study ◽  
Systemic Diseases ◽  
Glucose Levels ◽  
Dental Office ◽  
The Common ◽  
Finger Stick ◽  
Periodontal Probing

Abstract INTRODUCTION: Oral health plays an important role for screening of many systemic diseases. Hence, dentists play an important role in screening for systemic diseases as well. Early diagnosis of any systemic diseases can prevent long‑term complications. Diabetic is one of the common chronic diseases. Hence, the study had been undertaken to evaluate whether gingival crevicular blood (GCB) can be used to screen for diabetes during routine oral health checkups. MATERIAL AND METHODS: This analytical study included thirty participants who visited the Department of Periodontics, who fulfilled inclusion criteria and were willing to participate. Blood samples were collected by finger stick method and periodontal probing. The glucose levels of both the samples were estimated using glucometer and correlated the levels from both the methods. RESULTS: Correlation between capillary finger stick blood glucose and GCB glucose was high (0.97) and was significant at 0.01 level. CONCLUSION: Blood oozing during routine periodontal examination can be used for diabetes mellitus screening in dental office.

Effects of Adrenaline on the Dynamics of Carbohydrate Metabolism in Rats Treated Chronically with Adrenaline

1975 ◽  
Vol 53 (1) ◽  
pp. 124-128 ◽  
Author(s):  
Suzanne Rousseau-Migneron ◽  
Jacques LeBlanc ◽  
Louise Lafrance ◽  
Florent Depocas
Keyword(s):  
Blood Glucose ◽  
Clearance Rate ◽  
Glucose Production ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Control Group ◽  
Metabolic Clearance ◽  
Glucose Levels ◽  
Adrenaline Infusion ◽  
Initial Clearance

Following a subcutaneous injection of adrenaline (300 μg/kg), blood-glucose levels were lower in rats treated chronically with adrenaline (300 μg/kg twice a day for 28 days) than in control rats during at least 2.5 h after the injection. To explain this difference of response, the turnover rate of glucose was measured in control and adrenaline-treated rats during adrenaline infusion (0.75 μg/kg−1 min−1), with [U-14C]glucose as tracer. It was found that the rate of appearance of glucose was greater in the control than in the adrenaline-treated group after a 120-min infusion of adrenaline. The rate of disappearance of glucose in the treated rats increased during the first 60 min of infusion and stayed at this elevated level for a subsequent 2 h, whereas in the control rats, it remained unchanged at the beginning of adrenaline infusion and significantly increased only during the second and third hours of infusion. In addition, the metabolic-clearance rate of glucose was not modified by adrenaline in the treated group, but in the control group, the initial clearance rate was significantly less than in the treated group, and decreased during the first hour of adrenaline infusion even though blood glucose reached values of 244 mg/100 ml. From these data, it is suggested that rats adapt to a chronic exogenous supply of adrenaline by a reduced increase in glucose production in response to adrenaline infusion and a better glucose utilization, which possibly indicates a decrease in the inhibitory effect of adrenaline on insulin secretion.

scholarly journals Deletion of glycerol channel aquaporin-9 (Aqp9 ) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db ) obese mice

2015 ◽  
Vol 3 (9) ◽  
pp. e12538 ◽  
Author(s):  
Peter Spegel ◽  
Aakash Chawade ◽  
Søren Nielsen ◽  
Per Kjellbom ◽  
Michael Rützler
Keyword(s):  
Blood Glucose ◽  
Glucose Control ◽  
Leptin Receptor ◽  
Blood Glucose Control ◽  
Obese Mice ◽  
Aquaporin 9

scholarly journals MON-613 The Expression of TBC1 Domain Family, Member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nasser M Rizk ◽  
Amina Saleh ◽  
Abdelrahman ElGamal ◽  
Dina Elsayegh ◽  
Isin Cakir ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Skeletal Muscles ◽  
Glucose Disposal ◽  
Domain Family ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Blood Glucose Levels

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 &gt;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).

Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

1987 ◽  
Vol 253 (4) ◽  
pp. E435-E442 ◽  
Author(s):  
R. W. Stevenson ◽  
K. E. Steiner ◽  
G. K. Hendrick ◽  
A. D. Cherrington
Keyword(s):  
Carbohydrate Metabolism ◽  
Plasma Insulin ◽  
Control Period ◽  
Glucose Production ◽  
Glucose Levels ◽  
Glucose Clearance ◽  
Before And After ◽  
Initial Control ◽  
Lactate Uptake ◽  
Total Glucose

The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3-3H]glucose, glucose production (Ra) and utilization (Rd) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 microgram . kg-1 . min-1) was infused with intraportal replacement amounts of glucagon (0.42 ng . kg-1 . min-1) and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant (68 +/- 16 microU . kg-1 . min-1) for 250 min. Plasma glucagon was similar (84 +/- 14 and 89 +/- 19 pg/ml) before and during somatostatin infusion, while plasma insulin was lower (9.3 +/- 0.9 and 6.6 +/- 0.5 microU/ml, P less than 0.05). Plasma glucose levels remained similar (89 +/- 2 and 96 +/- 9 mg/dl), while Ra and Rd and the ratio of glucose clearance to plasma insulin were significantly (P less than 0.05) increased (from 2.18 +/- 0.12 to 3.21 +/- 0.35 and 2.30 +/- 0.09 to 3.26 +/- 0.38 mg . kg-1 . min-1, and 0.30 +/- 0.03 to 0.59 +/- 0.11, respectively). Net hepatic lactate uptake and [14C]alanine plus [14C]lactate conversion to [14C]glucose increased (P greater than 0.05) (from 9.32 +/- 0.47 to 16.54 +/- 2.97 mumol . kg-1 . min-1 and 100 to 263 +/- 37%, respectively). In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism.

scholarly journals Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor

2020 ◽  
Vol 21 (21) ◽  
pp. 7815
Author(s):  
Tomoko Okuyama ◽  
Jun Shirakawa ◽  
Kazuki Tajima ◽  
Yoko Ino ◽  
Heidrun Vethe ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Hepatic Steatosis ◽  
Insulin Signaling ◽  
Inflammatory Responses ◽  
Gene Expressions ◽  
Dual Inhibitor ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Hepatic Insulin Signaling ◽  
Igf1r Inhibitor

Abnormal hepatic insulin signaling is a cause or consequence of hepatic steatosis. DPP-4 inhibitors might be protective against fatty liver. We previously reported that the systemic inhibition of insulin receptor (IR) and IGF-1 receptor (IGF1R) by the administration of OSI-906 (linsitinib), a dual IR/IGF1R inhibitor, induced glucose intolerance, hepatic steatosis, and lipoatrophy in mice. In the present study, we investigated the effects of a DPP-4 inhibitor, linagliptin, on hepatic steatosis in OSI-906-treated mice. Unlike high-fat diet-induced hepatic steatosis, OSI-906-induced hepatic steatosis is not characterized by elevations in inflammatory responses or oxidative stress levels. Linagliptin improved OSI-906-induced hepatic steatosis via an insulin-signaling-independent pathway, without altering glucose levels, free fatty acid levels, gluconeogenic gene expressions in the liver, or visceral fat atrophy. Hepatic quantitative proteomic and phosphoproteomic analyses revealed that perilipin-2 (PLIN2), major urinary protein 20 (MUP20), cytochrome P450 2b10 (CYP2B10), and nicotinamide N-methyltransferase (NNMT) are possibly involved in the process of the amelioration of hepatic steatosis by linagliptin. Thus, linagliptin improved hepatic steatosis induced by IR and IGF1R inhibition via a previously unknown mechanism that did not involve gluconeogenesis, lipogenesis, or inflammation, suggesting the non-canonical actions of DPP-4 inhibitors in the treatment of hepatic steatosis under insulin-resistant conditions.

Increased epinephrine response and inaccurate glucoregulation in exercising athletes

1986 ◽  
Vol 61 (5) ◽  
pp. 1693-1700 ◽  
Author(s):  
M. Kjaer ◽  
P. A. Farrell ◽  
N. J. Christensen ◽  
H. Galbo
Keyword(s):  
Adrenal Medulla ◽  
Maximal Exercise ◽  
Nervous Activity ◽  
Glucose Production ◽  
Sympathetic Nervous Activity ◽  
Glucose Levels ◽  
Renal Threshold ◽  
Secretory Capacity ◽  
Stimulation Of

Epinephrine responses to insulin-induced hypoglycemia have indicated that athletes have a higher adrenal medullary secretory capacity than untrained subjects. This view was tested by an exercise protocol aiming at identical stimulation of the adrenal medulla in the two groups. Eight athletes (T) and eight controls (C) ran 7 min at 60% maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. Plasma epinephrine both at rest and at identical relative work loads [110% VO2max: 8.73 +/- 1.51 (T) vs. 3.60 +/- 1.09 mmol X l-1 (C)] was higher [P less than 0.05) in T than in C. Norepinephrine, as well as heart rate, increased identically in the two groups, indicating identical sympathetic nervous activity. Lactate and glycerol were higher in T than in C after running. Glucose production peaked immediately after exercise and was higher in T than in C. Glucose disappearance increased less than glucose production and was identical in T and C. Accordingly plasma glucose increased, more in T than in C (P less than 0.01). In T glucose levels approached the renal threshold greater than 20 min postexercise. Glucose clearance increased less in T than in C during exercise and decreased postexercise to or below (T, P less than 0.05) basal levels, despite increased insulin levels. Long-term endurance training increases responsiveness of the adrenal medulla to exercise, indicating increased secretory capacity. During maximal exercise this may contribute to higher glucose production, lower clearance, more inaccurate glucoregulation, and higher lypolysis in T compared with C.

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