Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.554 ◽

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 >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).

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Training improves glucose homeostasis in rats during exercise via glucose production

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.3.r770 ◽

1990 ◽

Vol 258 (3) ◽

pp. R770-R776 ◽

Cited By ~ 11

Author(s):

C. M. Donovan ◽

K. D. Sumida

Keyword(s):

Blood Glucose ◽

Glucose Homeostasis ◽

Glucose Production ◽

Rapid Decline ◽

Glucose Levels ◽

Glucose Carbon ◽

Blood Glucose Levels ◽

A Value ◽

Carbon Recycling ◽

Blood Glucose Concentrations

The effects of endurance training (running 1 h/day at 35 m/min, 10% grade) on glucose homeostasis during exercise (running 20 m/min) was studied in 30-h fasted rats. Primed-continuous infusion of [6-3H]- and [U-14C]glucose were employed to assess rates of appearance (Ra), disappearance (Rd), and apparent recycling. Training resulted in a 65% increase in skeletal muscle succinate dehydrogenase (SDH) activity but did not significantly influence body weight. Resting blood glucose concentrations were not significantly different between controls, 5.01 +/- 0.19 mM, and trained animals, 4.86 +/- 0.16 mM. Exercise resulted in a more rapid decline in blood glucose levels for control animals, reaching a value of 2.35 +/- 0.39 mM at 60 min, compared with 3.69 +/- 0.47 mM for trained animals. Glucose Ra was not significantly different between groups at rest, and rose for both groups during exercise. However, for controls Ra plateaued between 15 and 60 min of exercise at 11.03 +/- 0.73 mumol.100 g-1.min-1, whereas trained animals demonstrated a continuous rise to 17.13 +/- 1.18 mumol.100 g-1.min-1. Glucose Rd values were not significantly different between groups during the first 30 min of exercise but were significantly higher for trained animals during the final 30 min. As a result of the higher glucose Ra, trained animals demonstrated a smaller mean difference between Ra and Rd during exercise when compared with controls, -0.27 +/- 0.14 vs. -0.96 +/- 0.17 mumol.100 g-1.min-1. Trained animals further demonstrated significantly higher rates of glucose carbon recycling during the final 30 min of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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Association of Acrochordons with Diabetes Mellitus - A Hospital based Case Control Study

Nepal Medical Journal ◽

10.37080/nmj.147 ◽

2021 ◽

Vol 4 (1) ◽

pp. 51-60

Author(s):

Sunita Karki ◽

Anjan Rai ◽

Manish Pradhan

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Postprandial Glucose ◽

Early Screening ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Increased Risk ◽

Skin Tags ◽

And Gender ◽

Control Study

Introduction Acrochordons or skin tags are common benign cutaneous tumors that occur especially over the neck and major flexures. A possible association between diabetes mellitus and dyslipidemia is observed in numerous past studies with varying results. We aim to find out the association of diabetes mellitus with acrochordons Methods: One hundred patients were enrolled in our study. Among them, 50 (27 males and 23 females) with skin tags were selected as cases and 50 with other dermatologic diseases after matching age and gender were taken as controls. Blood glucose levels including both fasting and postprandial glucose levels were determined for both cases and controls and compared. Results: There was a higher frequency of Diabetes Mellitus and impaired glucose tolerance in patients with skin tags in comparison to controls (p<0.001). Moreover, there were higher odds of acquiring skin tags in patient with abnormal blood glucose levels. Conclusions: There is an increased risk of developing DM in patients with skin tags. It is highly recommended that suspicion for Diabetes Mellitus is to be done in patients with skin tags for early screening and diagnosis of Diabetes.

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Glycogen repletion following continuous and intermittent exercise to exhaustion

Journal of Applied Physiology ◽

10.1152/jappl.1980.49.4.722 ◽

1980 ◽

Vol 49 (4) ◽

pp. 722-728 ◽

Cited By ~ 49

Author(s):

G. A. Gaesser ◽

G. A. Brooks

Keyword(s):

Skeletal Muscle ◽

Blood Glucose ◽

Intermittent Exercise ◽

Lactate Concentration ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Complete Restoration ◽

Female Wistar Rats ◽

Endogenous Substrates ◽

Glycogen Repletion

Patterns of postexercise glycogen repletion in heart, skeletal muscle, and liver in the absence of exogenously supplied substrates during the first 4 h of recovery were assessed. Female Wistar rats were run to exhaustion using continuous (1.0 mph, 15% grade) and intermittent (alternate 1-min intervals at 0.5 and 1.5 mph, 15% grade) exercise protocols. Rats at exhaustion were characterized by marked depletion of glycogen in heart (55%), skeletal muscle (94%), and liver (97%). Blood glucose levels at exhaustion (1.33 mumol/g) were only 37% of preexercise levels. There were no significant differences between continuous and intermittent exercise groups for any of the tissue glycogen or blood glucose values. Cardiac muscle was the only tissue capable of complete restoration of glycogen levels while relying exclusively upon endogenous substrates. Concentrations of endogenous substrates present at the end of exercise were insufficient to support restoration of blood glucose levels to preexercise values nor support glycogen repletion in skeletal muscle and liver during the initial 4-h food-restricted postexercise period. With subsequent feeding, skeletal muscle demonstrated a glycogen supercompensation effect at 24 h (181.1 and 191.8% of preexercise levels for continuous and intermittent exercise, respectively). Lactate concentration in all tissues at the point exhaustion (1.5--2.5 times resting levels) were only moderately elevated and returned to preexercise levels within 15 min. It was concluded that lactate removal after exercise contributed only minimally to the repletion of muscle glycogen.

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Glucagon Deficiency Reduces Hepatic Glucose Production and Improves Glucose Tolerance In Adult Mice

Endocrine Reviews ◽

10.1210/edrv.31.4.9983 ◽

2010 ◽

Vol 31 (4) ◽

pp. 606-606

Author(s):

Aidan S. Hancock ◽

Aiping Du ◽

Jingxuan Liu ◽

Mayumi Miller ◽

Catherine L. May

Keyword(s):

Glucose Homeostasis ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Postprandial Glucose ◽

Glucagon Receptor ◽

Glucose Levels ◽

Adult Mice ◽

Hepatic Glucose ◽

Knockout Animals

Abstract The major role of glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of glucagon in the liver through attenuation of glucagon via glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the α-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic α-cell. Using this model, we found that glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of glucagon during the regulation of fasting and postprandial glucose homeostasis.

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Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.261.3.e304 ◽

1991 ◽

Vol 261 (3) ◽

pp. E304-E311 ◽

Cited By ~ 1

Author(s):

M. Walker ◽

G. R. Fulcher ◽

C. F. Sum ◽

H. Orskov ◽

K. G. Alberti

Keyword(s):

Fatty Acid ◽

Blood Glucose ◽

Glucose Uptake ◽

Whole Body ◽

Glucose Disposal ◽

Nonesterified Fatty Acid ◽

Nonesterified Fatty Acids ◽

Glucose Levels ◽

And Control ◽

Blood Glucose Concentrations

The purpose of this study was to examine the effect of physiological plasma nonesterified fatty acid (NEFA) levels on insulin-stimulated forearm and whole body glucose uptake and substrate oxidation during euglycemia and hyperglycemia. Seven healthy men received Intralipid and heparin for 210 min in two studies, with saline as control in two further studies. Insulin (0.05 U.kg-1.h-1) was infused from 60 min, and euglycemia was maintained during lipid (EL) and control (EC) studies, and hyperglycemia was maintained in the other studies (HL and HC). Forearm NEFA uptake was comparable in the lipid studies (+61 +/- 10 and +52 +/- 8 nmol.100 ml forearm-1.min-1, EL and HL) and was suppressed in the controls. With Intralipid, forearm glucose uptake decreased during euglycemia but not during hyperglycemia (+3.85 +/- 0.34 vs. +3.34 +/- 0.25 mumol.100 ml forearm-1.min-1, EC vs. EL, P less than 0.02), with comparable changes in whole body glucose uptake. Glucose oxidation and forearm alanine release decreased with Intralipid at both blood glucose levels, with no significant change in the rates of nonoxidative glucose disposal. These observations support the operation of the glucose-fatty acid cycle at physiological plasma NEFA levels at both blood glucose concentrations, but this was associated with a decrease in peripheral insulin sensitivity only during euglycemia.

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Role of PPAR in Hepatic Carbohydrate Metabolism

PPAR Research ◽

10.1155/2010/572405 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 36

Author(s):

Annelies Peeters ◽

Myriam Baes

Keyword(s):

Lipid Metabolism ◽

Blood Glucose ◽

Carbohydrate Metabolism ◽

Glucose Homeostasis ◽

Tight Control ◽

Master Regulator ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Ppar Ligands

Tight control of storage and synthesis of glucose during nutritional transitions is essential to maintain blood glucose levels, a process in which the liver has a central role. PPAR is the master regulator of lipid metabolism during fasting, but evidence is emerging for a role of PPAR in balancing glucose homeostasis as well. By using PPAR ligands and PPAR mice, several crucial genes were shown to be regulated by PPAR in a direct or indirect way. We here review recent evidence that PPAR contributes to the adaptation of hepatic carbohydrate metabolism during the fed-to-fasted or fasted-to-fed transition in rodents.

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Effect of Cinnamon Tea on Postprandial Glucose Concentration

Journal of Diabetes Research ◽

10.1155/2015/913651 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Maria Alexandra Bernardo ◽

Maria Leonor Silva ◽

Elisabeth Santos ◽

Margarida Maria Moncada ◽

José Brito ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Concentration ◽

Postprandial Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

High Blood Glucose ◽

Postprandial Period ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Oxidative Stress Status

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p< 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained fromC. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.

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Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice

Endocrinology ◽

10.1210/en.2018-00629 ◽

2018 ◽

Vol 160 (1) ◽

pp. 193-204 ◽

Cited By ~ 5

Author(s):

Isadora C Furigo ◽

Miriam F Suzuki ◽

João E Oliveira ◽

Angela M Ramos-Lobo ◽

Pryscila D S Teixeira ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Insulin Sensitivity ◽

Glucose Homeostasis ◽

Prolactin Secretion ◽

Dopamine Receptor Agonist ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Insulin Tolerance ◽

Promising Therapeutic Approach

Abstract Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance.

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Formulation and evaluation of anti-diabetic activity of repaglinide nanosuspension

International Journal of Pharmaceutical Research and Life Sciences ◽

10.26452/ijprls.v8i2.1208 ◽

2020 ◽

Vol 8 (2) ◽

pp. 17-21

Author(s):

Hemalatha S ◽

Monisha J

Keyword(s):

Blood Glucose ◽

Glucose Level ◽

Clinical Efficacy ◽

Oral Delivery ◽

Vascular Tissue ◽

Postprandial Glucose ◽

Postprandial Blood Glucose ◽

Particle Size Reduction ◽

Glucose Levels ◽

Blood Glucose Levels

Diabetes is one of those metabolic disorders that are typically characterized by an increase in blood glucose level, glycosuria and ketonemia. This widely spread disease and its complications result in thickening of vascular tissue, PVD, neuropathy and retinopathy. Repaglinide is the first member of the newer class of drugs that are designed to lower the postprandial glucose. The most prevalent problem faced by those drugs are very low solubility and thereby causing the oral delivery very inefficient leading to low bioavailability and improper dose and release proportionality. Research attempts are being put towards enhancing the oral bioavailability of repaglinide kind of lipophilic drugs to improve the clinical effect. Out of those methods to improve the solubility and bioavailability, Nano suspensions have been a promising method to facilitate the above problem. Nano suspensions can be applied to enhance the solubility of Repaglinide too. So, in this research, Repaglinide particle size reduction has been performed, and nanosuspensions were tested for their clinical efficacy invivo. A nanoprecipitation method was developed to prepare Repaglinide nanosuspension using poloxamer as a stabilizer. The prepared formulations had been tested for the clinical efficacy invivo in albino Wistar rats. The results showed that the nanosuspensions have been very efficient in lowering the postprandial blood glucose levels and also facilitated the consistent release of the drug, which is evident from the constant lowering of glucose level. The prepared nanosuspensions showed a very potent and found to clinically efficient compared to the pure drug and drug suspensions.

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