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

In patient with renal failure, hypoglycemia may develop because of decreased caloric intake, diminished renal insulin degradation and clearance, reduced renal gluconeogenesis and hepatic glucose production, impaired release of counter-regulatory hormone such as glucagon and epinephrine. We report here on a 80-year-old female patient with hypoglycemia due to endogenous hyperinsulinemia with acute kidney injury. She had chronic kidney disease and had no history of diabetes mellitus or insulin use. She had experienced recurrent hypoglycemia despite of intravenous dextrose injection and eventually generalized tonic clonic seizure occurred as a result of hypoglycemia. As serum creatinine level decreases, serum insulin and C-peptide level decreased and hypoglycemia was not occurred. We present this case along with a review of the literature.
Acute Kidney Injury ; Aged, 80 and over ; C-Peptide ; Creatinine ; Diabetes Mellitus ; Energy Intake ; Epinephrine ; Female ; Glucagon ; Gluconeogenesis ; Glucose ; Humans ; Hyperinsulinism ; Hypoglycemia* ; Insulin ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Seizures

BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.
AMP-Activated Protein Kinases ; Animals ; Diet ; Gluconeogenesis* ; Glucose ; Glucose-6-Phosphatase ; Hemoglobin A, Glycosylated ; Hyperglycemia ; Insulin Resistance* ; Insulin* ; Liver ; Mice* ; Models, Animal ; Muscle, Skeletal ; Phosphoenolpyruvate

Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs) were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.
Acetyltransferases ; Adipose Tissue ; Arginine* ; Brain ; Erythrocytes ; Fasting ; Gluconeogenesis ; Glucose* ; Homeostasis ; Liver ; Metabolism* ; Methyltransferases* ; Muscle, Skeletal ; Phosphoric Monoester Hydrolases ; Phosphotransferases ; Protein-Arginine N-Methyltransferases ; Transcription Factors