Advances in Metabolic Disorders

Volume 6

Rachmiel Levine, Rolf Luft

• Publisher: Academic Press
• Year: 2013
• ISBN:
  9781483215488
• Topic: Medicine
• Subtopic: Diseases & Allergies

Advances in Metabolic Disorders, Volume 6 covers the developments in the study of metabolic disorders. The book discusses the role of the skin in carbohydrate metabolism; the transmission of Alloxan diabetes and other diabetogenic influences; and the association between glucagon levels and diabetes mellitus. The text also describes the recent contributions to the study of diabetic angiopathy and neuropathy; the disorders due to enzyme defects in the red blood cell; and the pineal gland as a neuroendocrine inducer. The basic aspects of the biology and physiology of calcitonin in relation to its hitherto acknowledged significance in clinical metabolic disorders are also considered. Endocrinologists, biochemists, pharmacologists, physicians, physiologists and medical students will find the book invaluable.

The Role of the Skin in Carbohydrate Metabolism

John A. Johnson^* and Ramon M. Fusaro^†, ^*Departments of Dermatology and Biochemistry, University of Nebraska Medical Center, Omaha, Nebraska; ^†Department of Dermatology, University of Nebraska Medical Center, Omaha, Nebraska

Publisher Summary

This chapter provides an overview of the role of the skin in carbohydrate metabolism. The skin is a relatively large organ, which constitutes about 10% of the normal body weight. The major portion of the skin mass consists of dermis, which, in turn contains a large extracellular space. The metabolically active portion of skin, epidermis, derives much of its energy from the energetically inefficient process of anaerobic glycolysis. Consequently, skin converts large amounts of glucose to lactate that is discharged into the blood. Although skin exhibits features of carbohydrate metabolism other than utilization and turnover of glucose, these functions are of little quantitative importance in overall carbohydrate balance. The red blood cell, because of its ready availability, is useful in the study of metabolic disturbances, particularly in man whose internal tissues are usually not accessible for investigational purposes. Although skin relies heavily on glycolysis for its energy needs, the tissue displays most of the metabolic pathways that are observed in other organs.

I Introduction

II Properties of Skin

A Structure and Mass

B Characteristics of the Dermis

C Characteristics of the Epidermis

D Oxygen Tension in Skin

III The Role of the Dermis in Glucose Homeostasis

A Historical Aspects

B The Cutaneous Glucose Tolerance Test (CutGTT)

C Fates of Excess Dermal Glucose

IV Carbohydrate Metabolism of the Epidermis

A Enzymes Present in Epidermis

B Glucose Metabolism in the Epidermis

V Sources of Energy in the Epidermis

A Introduction

B Energy from Glucose Utilization

C Energy from Fatty Acid Oxidation

D Comments

VI Glucose/Lactate Balance in the Intact Animal

A The Skin Cori Cycle

B Glucose/Lactate Interconversion in the Intact Animal

C Lactate Balance in Oligemic Shock

D Lactate Production in the Gastrointestinal Tract

E Comments

VII The Skin as an Indicator of Impaired Carbohydrate Metabolism

A Introduction

B The Cutaneous Glucose Tolerance Test

C Glycogenoses

VIII Concluding Remarks

Addendum

References

I Introduction

The skin is a relatively large organ, constituting about 10% of the normal body weight. In the past the importance of this organ has been assessed in a physical sense. Thus, skin was shown to serve such important functions as protection of the animal from the environment, regulation of body temperature, and storage and release of water. The major portion of the skin mass consists of dermis, which in turn contains a large extracellular space. Hence, a fourth physical role may be assigned to skin: Temporary storage of glucose when blood glucose is elevated. On the other hand, the metabolically active portion of skin, epidermis, derives much of its energy from the energetically inefficient process of anaerobic glycolysis. Consequently, skin converts large amounts of glucose to lactate which is discharged into the blood. Thus it can be seen that the skin may play a passive (dermal) as well as an active (epidermal) role in the carbohydrate metabolism of the intact animal.

Although skin exhibits features of carbohydrate metabolism other than utilization and turnover of glucose (e.g., synthesis of mucopolysaccharides), these functions are of little quantitative importance in overall carbohydrate balance. We will therefore restrict our remarks to those aspects of skin carbohydrate metabolism that involve glucose and such metabolic derivatives as lactate and glycogen.

The red blood cell, because of its ready availability, is useful in the study of metabolic disturbances (Beutler, 1971), particularly in man whose internal tissues are usually not accessible for investigational purposes. Red cell metabolism, however, is almost exclusively glycolytic; and the tissue is therefore not useful as an indicator of the in vivo status of other metabolic pathways. In contrast, although skin relies heavily on glycolysis for its energy needs, the tissue displays most of the metabolic pathways observed in other organs. Pertinent information on the subject is not in the literature, but it seems likely that, in the intact animal, skin responds to hormonal and homeostatic influences as do other tissues. These features, coupled with ready accessibility, render skin the ideal tissue for physiological and biochemical studies in the intact animal, especially man. Unfortunately, this concept has not gained wide acceptance, and in vivo investigations of skin metabolism are consequently rare. A primary goal of this report is to alert the reader to the importance of skin in one aspect of body function, carbohydrate metabolism. To accomplish this we will review the physical role of skin in glucose homeostasis, the carbohydrate metabolism of skin, and the relationship of skin metabolism to carbohydrate balance in the intact animal. It is hoped that awareness of the interaction of skin with bodily function will prompt some readers to employ this useful tissue for meaningful in vivo investigations of many areas of human metabolism. Such studies might greatly supplement our knowledge in the etiology of disease, early diagnosis, and rationale of therapy.

II Properties of Skin

A Structure and Mass

The detailed anatomy of the skin has been presented by others (Montagna, 1962; Marples, 1965; Pillsbury, 1971), and it is sufficient here to briefly describe its major structural features. The skin consists of a massive, relatively inert dermis underlying the metabolically active epidermis. Though the dermis constitutes perhaps 95% of the mass of human skin, the epidermis accounts for most of the metabolic activity of the tissue. Several appendages—the hair follicle, sebaceous gland, and sweat gland—are metabolically important. These structures originate deep in the dermis and penetrate the epidermis to reach the skin surface. Metabolic studies are often performed with epidermal slices, which contain portions of the various appendages. However, since the latter share a common ectodermal origin with the epidermis (Flaxman, 1971) and appear to metabolize glucose in similar fashion, they may be considered part of the epidermal mass. Therefore, in subsequent discussions, comments on epidermal metabolism will often refer to the combined activities of the epidermis and its appendages.

The dermoepidermal interface is characterized by epidermal cones and ridges which project into the dermis. Corresponding dermal papillae project away from the dermis, and fit snugly into the valleys between the epidermal projections so that no empty space occurs between the two structures. The undulating interface provides a much greater contact area between dermis and epidermis than would be the case if they joined in a flat surface. The significance of this anatomic feature is apparent when one recognizes that the abundant blood supply of the skin is confined to the dermis. The epidermis therefore must obtain its nutrients and discharge its waste products by diffusion across the dermoepidermal interface.

Skin thickness varies with body site, and measures 2–3 mm in man. Of this, only a small portion (about 0.1 mm) is occupied by epidermis (Freeman et al, 1962). Various estimates of skin density and mass were reviewed earlier (Fusaro and Johnson, 1970). For the approximate calculations which will be employed in this report, we will use a figure of 10% of body weight (7 kg for a 70-kg man) for total skin mass. With a total skin surface area of 1.7 m² and density of 1.1 gm/cm³, the mass of epidermis (0.1 mm thick) is 190 gm.

B Characteristics of the Dermis

1 Blood Supply

The blood supply of the skin (dermis) far exceeds the nutritional needs of the epidermis. Each dermal papilla contains a capillary loop which arises from a subcapillary arterial plexus and returns to a corresponding venous plexus. Arteriovenous anastomoses are found, especially in areas where thermoregulation occurs. Opening and closing of these shunts provides a means of varying the cutaneous blood flow over a wide range, while blood flowing through the capillary loops provides uninterru...

Table of contents

• Cover image
• Title page
• Table of Contents
• Contributors to This Volume
• Copyright page
• Contributors
• Contents of Previous Volumes
• Chapter 1: The Role of the Skin in Carbohydrate Metabolism
• Chapter 2: On the Transmission of Alloxan Diabetes and other Diabetogenic Influences‡
• Chapter 3: Glucagon and Diabetes Mellitus
• Chapter 4: Recent Contributions to the Study of Diabetic Angiopathy and Neuropathy
• Chapter 5: Disorders Due to Enzyme Defects in the Red Blood Cell
• Chapter 6: The Pineal Gland—A Neuroendocrine Transducer
• Chapter 7: Calcitonin in Metabolic Disorders ‡
• Author Index
• Subject Index