Insulin resistance and diabetes combine to impair mitochondrial oxidative metabolism and cause lipid accumulation in non-adipose tissues such as skeletal muscles and the liver. The thyroid hormone stimulates thermogenesis, mitochondrial biogenesis, and various metabolisms, including gluconeogenesis and fatty-acid oxidation. Therefore, altered thyroid hormone action may induce the mitochondrial phenotype associated with insulin resistance. This review focuses on the correlation between thyroid hormone function and diabetes and the possible mechanisms associated with intracellular thyroid hormone dysfunction due to impaired metabolism.
Gluconeogenesis ; Insulin ; Insulin Resistance ; Liver ; Organelle Biogenesis ; Muscle, Skeletal ; Phenotype ; Thermogenesis ; Thyroid Gland

Few are familiar with the gluconeogenesis that occurs in the intestine under fasting or the influence of insulin. Recently, however, studies that revealed the function of intestinal gluconeogenesis as a regulatory process for glucose homeostasis and appetite were described. The intestine produces about 25% of total endogenous glucose during fasting and regulates energy homeostasis through communication with the brain. Glucose produced via intestinal gluconeogenesis is delivered to portal vein where periportal neural system senses glucose and sends a signal to the brain to regulate appetite and glucose homeostasis. Moreover, studies uncovered that intestinal gluconeogenesis contributes to the rapid metabolic improvements induced by gastric bypass surgery.
Appetite ; Bariatric Surgery ; Brain ; Fasting ; Gastric Bypass ; Gluconeogenesis ; Glucose* ; Homeostasis ; Insulin ; Intestines* ; Metabolism* ; Portal Vein

People whose diabetes is under good metabolic control should not experience more illness or infection than people without diabetes. However, when any illness occurs in someone with diabetes, the potential for hyperglycemia, hyperglycemia with ketosis, hyperglycemia with ketoacidosis, or hypoglycemia exists and requires education and treatment to prevent exacerbation or even possible death. In some parts of the world where access to medical care, insulin, or parenteral fluids is problematic, the added metabolic stress of an illness in someone with diabetes can be life threatening. Many illnesses are associated with higher levels of stress hormones which promote gluconeogenesis and insulin resistance. Education about the effects of concurrent illness ("sick days") is a critical component of diabetes management and must be adapted to the educational abilities and treatment possibilities of the particular situations in different parts of the world.
Diabetes Mellitus ; Gluconeogenesis ; Humans ; Hyperglycemia ; Hypoglycemia ; Insulin ; Insulin Resistance ; Ketosis ; Sick Leave ; Stress, Physiological

It is well known that the kidney is important for maintaining glucose homeostasis in vivo. However, the physiological role of the kidney in glucose metabolism is typically underestimated. Recently, a new class of anti-diabetic medications that affect the renal glucose regulatory mechanism was introduced into the market, sparking the interest of many researchers to better understand this mechanism. In this article, I briefly describe the role of the kidney in glucose metabolism and the changes of its function in patients with diabetes mellitus.
Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Gluconeogenesis ; Glucose* ; Homeostasis ; Humans ; Kidney* ; Metabolism*

As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway. Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction.
Mice ; Animals ; Metformin/pharmacology* ; Phosphoenolpyruvate Carboxykinase (ATP)/metabolism* ; Gluconeogenesis/genetics* ; Mice, Knockout

Glucose homeostasis is tightly regulated to meet the energy requirements of the vital organs and maintain an individual's health. The liver has a major role in the control of glucose homeostasis by controlling various pathways of glucose metabolism, including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis. Both the acute and chronic regulation of the enzymes involved in the pathways are required for the proper functioning of these complex interwoven systems. Allosteric control by various metabolic intermediates, as well as post-translational modifications of these metabolic enzymes constitute the acute control of these pathways, and the controlled expression of the genes encoding these enzymes is critical in mediating the longer-term regulation of these metabolic pathways. Notably, several key transcription factors are shown to be involved in the control of glucose metabolism including glycolysis and gluconeogenesis in the liver. In this review, we would like to illustrate the current understanding of glucose metabolism, with an emphasis on the transcription factors and their regulators that are involved in the chronic control of glucose homeostasis.
Gluconeogenesis ; Glucose* ; Glycogenolysis ; Glycolysis ; Homeostasis ; Liver ; Metabolic Networks and Pathways ; Metabolism* ; Negotiating ; Protein Processing, Post-Translational ; Transcription Factors

Alcohol influences glucose metabolism in both diabetic and non-diabetic individuals. Moderate alcohol consumption significantly decreases fasting glucose levels, but does not affect postprandial glucose levels. However, acute alcohol intake without food may provoke hypoglycemia. Moderate alcohol consumption may inhibit gluconeogenesis and enhance insulin sensitivity, but excessive alcohol intake (three or more drinks per day) may contribute to hyperglycemia. Daily alcohol intake in diabetics should be limited to a moderate amount (one drink per day or less for women and two drinks per day or less for men). Moderate alcohol intake may have cardiovascular benefits for patients with diabetes, but the trade-off between the cardiovascular benefits versus the potential risk of lower adherence associated with self-care behaviors should be considered.
Alcohol Drinking ; Blood Glucose ; Diabetes Mellitus ; Fasting ; Female ; Gluconeogenesis ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Insulin Resistance ; Self Care

Sleep-disordered breathing (SDB) is associated with increased cardiovascular and cerebrovascular morbidity. Epidemiological and clinic-based studies have shown that SDB is related to impaired glucose tolerance and increased insulin resistance, independent of obesity. Despite of a consistent association between SDB and impaired glucose-insulin metabolism, the mechanism underlying this relationship has not been fully elucidated. It is recognized that hypoxemia and hypercapnia that occur in SDB provoke sympathetic nervous activity and catecholamine, epinephrine and norepinephrine, and cortisol are released. Sympathetic hyperactivity and increased catecholamines can impair glucose homeostasis by increasing glycogenolysis and gluconeogenesis, which can result in increased circulating insulin levels and increased risk of insulin resistance. A prospective study is needed to investigate the causal relationship between SDB and impaired glucose-insulin metabolism in a healthy population without diabetes, hypertension and obesity as etiologic risk factors.
Anoxia ; Catecholamines ; Epinephrine ; Gluconeogenesis ; Glucose ; Glycogenolysis ; Homeostasis ; Hydrocortisone ; Hypercapnia ; Hypertension ; Insulin ; Insulin Resistance ; Metabolism ; Norepinephrine ; Obesity ; Risk Factors ; Sleep Apnea Syndromes* ; Sleep Wake Disorders

BACKGROUND: An important metabolic feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucose disposal which mediated by growth hormone hypersecretion. Octreotide, a synthetic octapeptide somatostatin analogue exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. This study was designed to ascertain the shorterm effect of octreotide on glucose tolerance in acromegaly. METHODS: 10 patients (five men and five women, age 47.9+/-11.8) were injected subcutaneously with octreotide, 100 micrograms for 24 hours. Patients were assessed with respect to growth hormone, glucose, and insulin response to a standard 100 g oral glucose tolerance test (OGTT) before and during the last 2 hour of octreotide infusion. RESULTS: During the therapy, there was significant decrease in mean blood glucose response to OGTT (678.4+/-51.9 vs 581.9+/-47.3 mg/dL/2hr: mean areas under the glucose curve, p=0.01) and mean serum insulin response to oral glucose load was significantly reduced in all patients (339.2+/-106.2 vs 256.7+/-111.3 U/mL/2hr: mean areas under the insulin curve, p=0.01). Using glucose tolerance test criteria three patients of 10 had normal glucose tolerance, four and three had impaired glucose tolerance and diabetes, respectively, at base line. While on octreotide these composition was changed to six patients of NGT, three of IGT and one diabetes. CONCLUSION: We conclude that insulin resistance mediated by GH hypersecretion was improved by shorterm octreotide treatment.
Acromegaly* ; Blood Glucose ; Female ; Gluconeogenesis ; Glucose Tolerance Test ; Glucose* ; Growth Hormone ; Homeostasis ; Humans ; Infusions, Subcutaneous* ; Insulin ; Insulin Resistance ; Male ; Octreotide* ; Social Control, Formal ; Somatostatin

Glucose is essential for energy metabolism in human, especially in brain, and is a source of energy storage in the form of glycogen, fat and protein. During fetal life, the predominant source of energy is also glucose, which crosses the placenta by facilitated diffusion. There is very little endogenous glucose production under normal circumstances during fetal life. During labor, the fetus is exposed to physiological challenges that require metabolic adaptation. A healthy infant successfully manages the postnatal transition by mobilizing and using alternative. After birth, there is a rapid surge in catecholamine and glucagon levels, and a steady decrease in insulin, as blood glucose levels decline. These hormonal changes induce enzyme activities that lead to glycogenolysis and gluconeogenesis. During the first 24-48 hours of life, plasma glucose concentrations of neonates are typically lower than later in life. Distinguishing between transitional neonatal glucose regulation in normal neonates and hypoglycemia that persists or occurs for the first time beyond the first 72 hours of life is important for prompt diagnosis and treatment to avoid serious consequences.
Blood Glucose ; Brain ; Diagnosis ; Energy Metabolism ; Facilitated Diffusion ; Fetus ; Glucagon ; Gluconeogenesis ; Glucose* ; Glycogen ; Glycogenolysis ; Homeostasis* ; Humans ; Hypoglycemia ; Infant ; Infant, Newborn ; Insulin ; Parturition ; Placenta