Coalescence and directed anisotropic growth of starch granule initials in subdomains of Arabidopsis thaliana chloroplasts

Living cells orchestrate enzyme activities to produce myriads of biopolymers but cell-biological understanding of such processes is scarce. Starch, a plant biopolymer forming discrete, semi-crystalline granules within plastids, plays a central role in glucose storage, which is fundamental to life. Combining complementary imaging techniques and Arabidopsis genetics we reveal that, in chloroplasts, multiple starch granules initiate in stromal pockets between thylakoid membranes. These initials coalesce, then grow anisotropically to form lenticular granules. The major starch polymer, amylopectin, is synthesized at the granule surface, while the minor amylose component is deposited internally. The non-enzymatic domain of STARCH SYNTHASE 4, which controls the protein’s localization, is required for anisotropic growth. These results present us with a conceptual framework for understanding the biosynthesis of this key nutrient.

Interactions between insulin and exercise

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

Main Organs Involved in Glucose Metabolism

Sugar, or technically known as glucose, is the main source of energy of all cells in the human body. The glucose homeostasis cycle is the mechanism to maintain blood glucose levels in a healthy threshold. When this natural mechanism is broken, many metabolic disorders appear such as diabetes mellitus, and some substances of interest, like glucose, are out of control. In the mechanism to maintain blood glucose, several organs are involved but the role of most of them has been disregarded in the literature. In this chapter, the main organs involved in such a mechanism and their role in glucose metabolism are described. Specifically, the stomach and small intestine, organs of the gastrointestinal system, are the first to play an important role in the regulatory system, because it is where carbohydrates are digested and absorbed as glucose into the bloodstream. Then glucose as a simple substance goes to the liver to be stored as glycogen. Glucose storage occurs due to the delivery of hormones from the pancreas, which produces, stores, and releases insulin and glucagon, two antagonistic hormones with an important role in glucose metabolism. The kidneys assist the liver in insulin clearance in the postprandial state and gluconeogenesis in the post absorptive state. Physiological aspects and the detailed role of every organ involved in glucose metabolism are described in this chapter.

Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes

Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca2+]cytosol. 42% of MHS patients have hyperglycemia. We show that phosphorylated glycogen phosphorylase (GPa), glycogen synthase (GSa) – respectively activated and inactivated by phosphorylation – and their Ca2+-dependent kinase (PhK), are elevated in microsomal extracts from MHS patients’ muscle. Glycogen and glucose transporter GLUT4 are decreased. [Ca2+]cytosol, increased to MHS levels, promoted GP phosphorylation. Imaging at ~100 nm resolution located GPa at sarcoplasmic reticulum (SR) junctional cisternae, and apo-GP at Z disk. MHS muscle therefore has a wide-ranging alteration in glucose metabolism: high [Ca2+]cytosol activates PhK, which inhibits GS, activates GP and moves it toward the SR, favoring glycogenolysis. The alterations probably cause these patients’ hyperglycemia. For basic studies, MHS emerges as a variable stressor, which forces glucose pathways from the normal to the diseased range, thereby exposing novel metabolic links.

The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis

: Autophagy plays a role in several physiological and pathological processes as it controls the turnover rate of cellular components and influences cellular homeostasis. The liver plays a central role in controlling organisms’ metabolism, regulating glucose storage, plasma proteins and bile synthesis and the removal of toxic substances. Liver functions are particularly sensitive to autophagy modulation. In this review we summarize studies investigating how autophagy influences the hepatic metabolism, focusing on fat accumulation and lipids turnover. We also describe how autophagy affects bile production and the scavenger function within the complex homeostasis of the liver. We underline the role of hepatic autophagy in counteracting the metabolic syndrome and the associated cardiovascular risk. Finally, we highlight recent reports demonstrating how the autophagy occurring within the liver may affect skeletal muscle homeostasis as well as different extrahepatic solid tumors, such as melanoma.

Glycogen Storage Diseases

Glycogen storage diseases result from deficiencies of various enzymes or proteins in the pathways of glycogen metabolism. The reduction in effective glucose storage and/or mobilization results in hypoglycemia and accumulation of glycogen in tissues. Diagnosis can occur at any age, from infancy to adulthood, depending on the pathway affected and the degree of enzyme deficiency. The clinical presentation varies, but the most commonly affected organ systems include the heart, liver, and skeletal muscles. In addition to the morbidity that can occur from dysfunction of these organs, important anesthetic implications include administration of glucose-containing fluids to avoid hypoglycemia, monitoring for acidosis, and caution with use of depolarizing muscle relaxants because of the potential risk of hyperkalemia and rhabdomyolysis. Inheritance is commonly autosomal recessive.

Adaptations to excess choline in insulin resistant and Pcyt2 deficient skeletal muscle

It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2+/−) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2+/− mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2+/− mice, treated Pcyt2+/− mice, and Pcyt2+/+ mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2+/− muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.