2018, Blackburn College, Inog's review: "Cialis Sublingual 20 mg. Best online Cialis Sublingual.".
Several of these gastrointestinal peptides such as GLP-1 and GIP do not act as direct insulin secretagogues when blood glucose levels are normal but do so after a meal large enough to cause an increase in the blood glucose concen- tration cheap 20mg cialis sublingual mastercard. The release of these peptides may explain why the modest postprandial increase in serum glucose seen in normal subjects has a relatively robust stimulatory effect on insulin release order cialis sublingual 20mg with visa, whereas a similar glucose concentration in vitro elicits a signifi- cantly smaller increase in insulin secretion. Likewise, this effect (certain factors potentiating insulin release), known as the “incretin effect,” could account for the greater beta cell response seen after an oral glucose load as opposed to that seen after the administration of glucose intravenously. Gastrointestinal-Derived Hormones Directly Affecting Fuel Metabolism Primary Cell/ Secretory Stimuli Hormone Tissue of Origin Actions (and Inhibitors) Amylin Pancreatic beta cell, endocrine 1. Inhibits arginine-stimulated and Co-secreted with insulin in cells of stomach and small postprandial glucagon secretion response to oral nutrients intestine 2. Inhibits insulin secretion Calcitonin gene-related Enteric neurons and Inhibits insulin secretion Oral glucose intake and gastric peptide (CGRP) enteroendocrine cells of the acid secretion rectum Galanin Nervous system, pituitary, Inhibits secretion of insulin, Intestinal distension neurons of gut, pancreas, somatostatin, enteroglucagon, thyroid, and adrenal gland pancreatic polypeptide, and others Gastric inhibitory polypeptide/ Neuroendocrine K cells of 1. Increases insulin release via an Oral nutrient ingestion, especially glucose-dependent duodenum and proximal "incretin" effect long-chain fatty acids insulinotropic polypeptide (GIP) jejunum 2. Regulates glucose and lipid metabolism Gastrin-releasing peptide (GRP) Enteric nervous system and Stimulates release of pancreas cholecystokinin; GIP, gastrin, glucagon, GLP-1, GLP-2, and somatostatin Ghrelin Central nervous system, Stimulates growth hormone release Fasting stomach, small intestine, and colon Glucagon Pancreatic alpha cell, central Primary counter-regulatory hormone Neural and humoral factors nervous system that restores glucose levels in released in response to hypoglycemic state (increases hypoglycemia glycogenolysis and gluconeogenesis as well as protein-lipid flux in liver and muscle) Glucagon-like peptide-1 (GLP-1) Enteroendocrine L cells in 1. Oral nutrient ingestion ileum, colon, and central meals by inhibiting glucagon 2. Vagus nerve nervous system secretion and stimulating insulin 3. Acts through second messengers in beta cells to increase sensitivity of these cells to glucose (an incretin) Glucagon-like peptide-2 (GLP-2) The same as for GLP-1 Stimulates intestinal hexose Same as GLP-1 transport Neuropeptide Y Central and peripheral nervous Inhibits glucose-stimulated insulin Oral nutrient ingestion and system, pancreatic islet cells secretion activation of sympathetic nervous system Neurotensin (NT) Small intestinal N cells In brain, modulates dopamine 1. Luminal lipid nutrients (especially ileum), enteric neurotransmission and anterior 2. Somatostatin inhibits secretion gland, pancreas Pituitary adenylate cyclase Brain, lung, and enteric nervous Stimulates insulin and Activation of central nervous activating peptide (PACAP) system catecholamine release system Somatostatin Central nervous system, 1. Luminal nutrients pancreatic delta cells, and glucagon and PP (islets), and gas- 2. GLP-1 enteroendocrine delta cells trin, secretin, GLP-1, and 3. Beta-adrenergic stimulation Vasoactive intestinal peptide Widely expressed in the central May regulate release of insulin and 1. Mechanical stimulation of gut (VIP) and peripheral nervous pancreatic glucagon 2. Activation of central and systems peripheral nervous systems CHAPTER 43 / ACTIONS OF HORMONES THAT REGULATE FUEL METABOLISM 801 Table 43. Gastrointestinal-Derived Hormones Indirectly Affecting Fuel Metabolism Primary Cell/ Secretory Stimuli Hormone Tissue of Origin Actions (and Inhibitors) Cholecystokinin (CCK) Enteroendocrine I cells, enteric 1. Regulates nutrient-stimulated enzyme secretion and gallbladder contraction 4. Increases postprandial satiety Gastrin Enteroendocrine G cells of the Induces gastric acid secretion 1. Luminal contents, especially stomach, duodenal bulb, and aromatic amino acids, cal- other cells cium, coffee, and ethanol 2. Vagus nerve stimulation; activation of beta-adrenergic and GABA neurons 3. Somatostatin inhibits secretion Motilin Enteroendocrine M cells in 1. Duodenal alkalinization upper small bowel and other stomach 5. Secretion suppressed by pancreatic enzyme secretion nutrients in duodenum 3. Induces gallbladder contraction Pancreatic polypeptide (PP) Endocrine cells in periphery of 1. Reduces CCK-mediated gastric acid Stimulated by intraluminal nutri- islets in the head of the secretion ents, hypoglycemia, and pancreas 2. Increases intestinal transit time (slows vagal nerve stimulation motility) Peptide YY (PYY) Enteroendocrine cells, 1. Oral nutrient ingestion developing pancreas; alpha gastric motility 2. Bile acids and fatty acids cells in mature islets 2. Inhibits pancreatic exocrine secretion Secretin Enteroendocrine S cells in 1. Gastric acid, bile salts, fatty upper small bowel bicarbonate and water secretion acids, peptides, and ethanol 2. Inhibits postprandial gastric emptying, gastrin release, and gastric acid secretion Tachykinins Neurons localized in the sub- 1. Regulates vasomotor and gastroin- Direct and indirect activation of mucous and myenteric testinal smooth muscle contraction neurons in submucosa and plexuses; enterochromaffin 2. Mucus secretion and water absorption myenteric plexuses in gut cells in gut epithelium epithelium Thyrotropin-releasing Enteric nervous system, colon, 1. Suppresses hormone-stimulated In the stomach, histamine and hormone (TRH) G cells of stomach, and gastric acid secretion serotonin stimulate secretion pancreatic beta cell 2. Inhibits cholesterol synthesis within the intestinal mucosa G.
In addition buy discount cialis sublingual 20 mg online, the orthopaedist should have a general understanding of the local special education system in which he is practicing trusted 20mg cialis sublingual. By nature of the special education system as it is defined in the federal code, there are many areas of frequent conflict that involve the or- thopaedist directly. Separation of Education and Medical Practice Education and medical practice are separate in our society at almost every level, and this separation has led to frequent conflicts in the area of special 5. Therapy, Education, and Other Treatment Modalities 169 education. More specifically, special education law states that the educa- tional system must pay for medical evaluations that are needed to determine children’s educational goals and functions. The school system has to provide adaptive devices that are needed for children to gain an educational experi- ence; however, the educational system does not need to purchase medical treatment required to maximize children’s educational goals. The eye exam- ination is a typical examination that the educational system is required to perform because visual acuity may be a major obstacle to a child’s learning ability. If the eye examination demonstrates that the child needs eyeglasses, the school system has to pay for the glasses if the glasses are interpreted to be adaptive devices. However, if the glasses are interpreted to be medical de- vices, the educational system does not pay. This exact example has been lit- igated in several locations in various courts, and decisions have been handed down in both directions. These types of circumstances have spawned a whole legal subspecialty to help interpret and litigate areas of special education law. What Is Medical Equipment and What Is an Adaptive Device? The definition from the perspective of the educational system of what is ed- ucational and what is medical varies from state to state and even from school district to school district based on many reasons. Financial considerations in the educational system are often part of the reason to determine how ag- gressively the educational system pursues trying to shift costs to the medical payers. In general, wheelchairs, walking aids, and orthotics are considered medical equipment. Special desk seating, communication devices, writing aids, standers, and positioning devices used by children at school are con- sidered educational devices. Devices such as standers or other adaptive equipment such as tricycles that children can also use at home may fall into either category. Prescriptions A major impact on the pediatric orthopaedist who manages children with CP is the need for many prescriptions, especially related to their needs in school. Although there is variability from state to state, most states require licensed therapists to provide therapeutic services only under a doctor’s or- der. With this requirement, even therapists practicing in a school environ- ment doing therapy to further children’s education need to have a physician’s prescription. If that prescription comes from an orthopaedist and is very spe- cific for range of motion, gait training, or postoperative rehabilitation needs, with specific frequency requirements, the school administration can legiti- mately conclude that it is medically needed rehabilitation therapy and refuse to provide the services. The prescription that works best in the school envi- ronment is to order educationally based therapy and include specific restric- tions and suggestions, such as a child’s need to be in a stander every day for a certain maximum period of time. The physician needs to understand his proper role as related to the edu- cational system. The physician also needs to be able to clearly articulate that role to parents. A common parental concern is that the school is not pro- viding adequate therapy to their child. In some situations this concern is true, and in others, the parents’ enthusiasm for therapy and the expectations of how much benefit the therapy will provide are misunderstood. The ortho- paedist should play a role in explaining to the parents that therapy is not indicated if that is his opinion, but he can also explain his role in ordering school therapy when he believes more therapy is required but the school 170 Cerebral Palsy Management disagrees. The parents’ usual response to the physician is, “You wrote the prescription, so the school has to do what you said. In general, a child with this level of motor function probably has more long-term side effects from therapy than benefits, especially if the therapy interferes with any academic classroom work. In this situation, the parents need to be educated and the school decision needs to be reinforced with the parents. The opposite example occurs with a middle school child with severe quadriplegia, who has made no motor gains over several years, and the school IEP plans to maintain motor function with classroom activities pro- vided by a teacher and a schoolroom teacher’s aide. The educator believes that the focus of the this child’s educational goals should be teaching him to use augmentative communication. These are difficult subjective decisions and the orthopaedist may find himself siding with the parents; however, an aggressive response by letter or phone call will not help the parents’ position because it will only give the school administration physical evidence that this need is medical rehabilita- tion. It is much more helpful for the orthopaedist to recognize that this is an educational decision, and offer the parents and school additional data as a way of helping the school and parents negotiate the disagreement. This ne- gotiation will be more profitable with this approach than getting involved with a litigation. Another major area where prescription need arises is obtaining adaptive equipment. All adaptive equipment purchased through medical reimburse- ment sources, such as private insurance or Medicaid, must include a medical prescription and usually a letter of medical need. Examples include orthotics, wheelchairs, and standers. If devices are purchased with educational dollars, no prescriptions are needed; these would typically include writing desks and computers used as augmentative writing devices. Many devices fall in be- tween, such as augmentative communication, classroom standers, and floor positioning devices. The specifics of who pays for what may be negotiated at the state level between agencies, or in other states, debated at length, often to the major advantage only of the legal profession. Physician–Educator Relationship In almost all school environments in special education, administrators really try to provide the best services for the children in their care.
However cialis sublingual 20 mg overnight delivery, as insulin levels drop order 20 mg cialis sublingual mastercard, the concentration of GLUT4 transporters in the membrane is reduced, thereby reducing glucose entry from the cir- Muscle GLUT4 transporters also culation into the muscle. Thus, if produces NADH and acetyl CoA, which slow the flow of carbon from glucose energy levels are very low, and AMP levels through the reaction catalyzed by pyruvate dehydrogenase (see Fig. Thus, the increase, glucose can still be transported oxidation of fatty acids provides a major portion of the increased demand for ATP from the circulation into the muscle to pro- generation and spares blood glucose. THE IMPORTANCE OF AMP AND FRUCTOSE 2,6-BISPHOSPHATE The switch between catabolic and anabolic pathways is often regulated by the lev- els of AMP and fructose 2,6-bisphosphate in cells, particularly the liver. As a cell uses ATP in energy-requiring path- ways, the levels of AMP accumulate more rapidly than that of ADP because of the adenylate kinase reaction (2 ADP S ATP and AMP). The rise in AMP levels then signals that more energy is required (usually through allosteric binding sites on enzymes and the activation of the AMP-activated protein kinase), and the cell will switch to the activation of catabolic pathways. As AMP levels drop, and ATP levels rise, the anabolic pathways are now activated to store the excess energy. CHAPTER 36 / INTEGRATION OF CARBOHYDRATES AND LIPID METABOLISM 677 The levels of fructose 2,6-bisphosphate are also critical in regulating glycolysis versus gluconeogenesis in the liver. Under conditions of high blood glucose, and insulin release, fructose 2,6 bisphosphate levels will be high because PFK-2 will be in its activated state. The fructose 2,6 bisphosphate activates PFK-1, and inhibits fructose 2,6 bisphosphatase, thereby allowing glycolysis to proceed. When blood glucose levels are low, and glucagon is released, PFK-2 is phosphorylated by the cAMP-dependent protein kinase and is inhibited, thereby lowering fructose 2,6-bisphosphate levels and inhibiting glycolysis, while favoring gluconeogenesis. CLINICAL COMMENTS Bea Selmass’s younger sister was very concerned that Bea’s pancreatic tumor might be genetically determined or potentially malignant, so she accompanied Bea to her second postoperative visit to the endocrinologist. The doctor explained that insulinomas may be familial in up to 20% of cases and that in 10% of patients with insulinomas, additional secretory neoplasms may occur in the anterior pituitary or the parathyroid glands (a genetically determined syn- drome known as multiple endocrine neoplasia, type I or, simply, MEN I). Bea’s tumor showed no evidence of malignancy, and the histologic slides, although not always definitive, showed a benign-appearing process. The doctor was careful to explain, however, that close observation for recurrent hypoglycemia and for the signs and symptoms suggestive of other facets of MEN I would be necessary for the remainder of Bea’s and her immediate family’s life. Diabetes mellitus is a well-accepted risk factor for the development of coronary artery disease; the risk is three to four times higher in the dia- betic than in the nondiabetic population. Although chronically elevated serum levels of chylomicrons and VLDL may contribute to this atherogenic pre- disposition, the premature vascular disease seen in Di Abietes and other patients with type 1 diabetes mellitus, as well as Ann Sulin and other patients with type 2 diabetes mellitus, is also related to other abnormalities in lipid metabolism. Because Di Abietes produces very Among these are the increase in glycation (nonenzymatic attachment of glucose little insulin, she is prone to develop- molecules to proteins) of LDL apoproteins as well as glycation of the proteins of ing ketoacidosis. When insulin levels the LDL receptor, which occurs when serum glucose levels are chronically ele- are low, HSL of adipose tissue is very active, vated. These glycations interfere with the normal interaction or “fit” of the cir- resulting in increased lipolysis. The fatty acids culating LDL particles with their specific receptors on cell membranes. As a con- that are released travel to the liver, where they are converted to the triacylglycerols of VLDL. The LDL particles, therefore, remain in the circulation and eventu- to ketone bodies. If Di does not take exoge- ally bind nonspecifically to “scavenger” receptors located on macrophages adja- nous insulin or if her insulin levels decrease cent to the endothelial surfaces of blood vessels, one of the early steps in the abruptly for some physiologic reason, she may process of atherogenesis. For reasons that are not as well under- BIOCHEMICAL COMMENTS stood, individuals with type 2 diabetes melli- tus, such as Ann Sulin, do not tend to All of the material in this chapter was presented previously. One possible explana- because this information is so critical for understanding biochemistry in a tion is that the insulin resistance is tissue- specific; the insulin sensitivity of adipocytes way that will allow it to be used in interpreting clinical situations, it was may be greater than that of muscle and liver. In addition, the information previously presented under Such a tissue-specific sensitivity would lead carbohydrate metabolism was integrated with lipid metabolism. We have, for the most to less fatty acids being released from part, left out the role of allosteric modifiers and other regulatory mechanisms that adipocytes in type 2 diabetes than in type 1 finely coordinate these processes to an exquisite level. Because such details may be diabetes, although in both cases the release important for specific clinical situations, we hope this summary will serve as a frame- of fatty acids would be greater than that of work to which the details can be fitted as students advance in their clinical studies. Pi GK Ca2+ UTP PP 2P i i (hi Km) NADPH UDP–Glucose Liver Blood G–6– –1–P Pi + Insulin Ribulose–5–P P UDP GS GS– P i F–6– i + cAMP VLDL ATP + F2,6P F2,6P – Glycogen PFK + AMP AMP Phos a + Insulin IDL cAMP PhK– P P F1,6P + P Phos b i Lysosome LDL Glycerol Pi VLDL PhK + Insulin CO PEP + cAMP B Apoprotein 2 Phospho- PK PK– P Steroid lipids + Insulin hormones GDP Alanine Pyruvate Lactate Cholesterol Bile acids TG + NADH NAD CO2 Insulin PEP– CK Cholesterol GTP NADPH FACoA Bile salts KB FACoA + HMG-CoA NADP Palmitate Malonyl NADPH Pyruvate – CoA Malonyl CoA + Insulin Malate CO2 OAA HMG-CoA KB + Insulin PDH– P PDH Citrate + – NADH AcC AcC– P Acetyl CoA FADH2 OAA + FACoA + cAMP NADH – OAA Citrate Acetyl CoA + Asp Asp NADH NAD Malate Malate Isocitrate Citrate – NADH αKG + ADP Glycerol FA Induction + Activation Repression – Inhibition Adipose TG Fig. Regulation of carbohydrate and lipid metabolism in the liver. Solid blue arrows indicate the flow of metabolites in the fed state. Solid black arrows indicate the flow during fasting. G glucose; GK glucokinase; F fructose; PFK phosphofructokinase-1; PEP phosphoenolpyru- vate; PK pyruvate kinase; OAA oxaloacetate; KG -ketoglutarate; GS glycogen synthase; Phos glycogen phosphorylase; PhK phos- phorylase kinase; AcC acetyl CoA carboxylase; FA fatty acid or fatty acyl group; TG triacylglycerol; circled P phosphate group. This figure and tables should help students to integrate this mass of material. Now that many of the details of the pathways have been presented, it would be worthwhile to re-read the first three chapters of this book. A student who understands biochemistry within the context of fuel metabolism is in a very good position to solve clinical problems that involve metabolic derangements. CHAPTER 36 / INTEGRATION OF CARBOHYDRATES AND LIPID METABOLISM 679 Table 36. Flowchart of Changes in Liver Metabolism When blood sugar increases: When blood sugar decreases: Insulin is released, which leads Glucagon is released, which to the dephosphorylation of: leads to the phosphorylation of: • PFK-2 (now active) • PFK-2 (now inactive) • Pyruvate kinase (now active) • Pyruvate kinase (now inactive) • Glycogen synthase (now active) • Glycogen synthase (now inactive) • Phosphorylase kinase (now inactive) • Phosphorylase kinase (now active) • Glycogen phosphorylase (now inactive) • Glycogen phosphorylase (now active) • Pyruvate dehydrogenase (now active) • Pyruvate dehydrogenase (now inactive) • Acetyl CoA Carboxylase (now active) • Acetyl CoA Carboxylase (now inactive) Which leads to active Which leads to active • Glycolysis • Glycogenolysis • Fatty acid synthesis • Fatty acid oxidation • Glycogen synthesis • Gluconeogenesis Table 36. Regulation of Liver Enzymes Involved in Glycogen, Blood Glucose, and Triacylglycerol Synthesis and Degradation LIVER ENZYMES REGULATED BY ACTIVATION/INHIBITION Enzyme Activated By State in Which Active Phosphofructokinase-1 Fructose-2,6-bisP, AMP Fed Pyruvate carboxylase Acetyl CoA Fed and fasting Acetyl CoA carboxylase Citrate Fed Carnitine: Loss of inhibitor Fasting palmitoyltransferase I (malonyl CoA) LIVER ENZYMES REGULATED BY PHOSPHORYLATION/DEPHOSPHORYLATION Enzyme Active Form State in Which Active Glycogen synthase Dephosphorylated Fed Phosphorylase kinase Phosphorylated Fasting Glycogen phosphorylase Phosphorylated Fasting Phosphofructokinase-2/F-2, Dephosphorylated Fed 6-bisphosphatase (acts as a kinase, increasing fructose- 2,6-bisP levels) Phosphofructokinase-2/F-2, Phosphorylated Fasting 6-bisphosphatase (acts as a phosphatase, decreasing fructose- 2,6-bisP levels) Pyruvate kinase Dephosphorylated Fed Pyruvate dehydrogenase Dephosphorylated Fed Acetyl CoA carboxylase Dephosphorylated Fed LIVER ENZYMES REGULATED BY INDUCTION/REPRESSION Enzyme State in Which Induced Process Affected Glucokinase Fed Glucose S TG Citrate lyase Fed Glucose S TG Acetyl CoA carboxylase Fed Glucose S TG Fatty acid synthase Fed Glucose S TG Malic enzyme Fed Production of NADPH Glucose-6-P Fed Production of NADPH dehydrogenase Glucose 6-phosphatase Fasted Production of blood glucose Fructose 1, Fasted Production of blood glucose 6-bisphosphatase Phosphoenolpyruvate Fasted Production of blood glucose carboxykinase 680 SECTION SIX / LIPID METABOLISM Suggested References Iritani N. Nutritional and hormonal regulation of lipogenic-enzyme gene expression in rat liver. Regulation of expression of glucose transporters by glucose: a review of studies in vivo and in cell cultures.
10 of 10 - Review by C. Sobota
Votes: 54 votes
Total customer reviews: 54