Human Physiology, 14th edition (2016)

Regulation of Metabolism 681

glucose concentration is too high ( mellitus is derived from a

Latin word meaning “honeyed” or “sweet”). The general term

diabetes comes from a Greek word meaning “siphon;” it refers

to the frequent urination associated with this condition. The

hyperglycemia of diabetes mellitus results from either the insuf-

ficient secretion of insulin by the beta cells of the pancreatic

islets or the inability of secreted insulin to stimulate the cellular

uptake of glucose from the blood. Diabetes mellitus, in short,

results from the inadequate secretion or action of insulin. There

is also elevated glucagon secretion, because insulin is less able to

allow a high plasma glucose concentration to suppress the secre-

tion of glucagon. Evidence suggests that glucagon (through its

stimulation of hepatic glycogenolysis) contributes significantly

to the hyperglycemia of people with type 2 diabetes mellitus

(discussed shortly).

There are two major forms of diabetes mellitus. In type 1

(or insulin-dependent ) diabetes, the beta cells are progres-

sively destroyed and secrete little or no insulin. Injections of

exogenous insulin are thus required to sustain the person’s life

(since insulin is a polypeptide, it would be digested if taken

orally). However, there is an inhaler containing a fine powder

of insulin available to adults with type 1 diabetes. Also, instead

of periodic insulin injections, many diabetics instead use an

insulin pump, which continuously infuses insulin subcutane-

ously at a slow rate, augmented by the patient activating a con-

trol unit to provide a calculated boost (bolus) of insulin after

carbohydrate meals. Type 1 diabetes accounts for about 5% to

10% of the diabetic population.

Most diabetics have type 2 ( non-insulin-dependent ) diabetes.

Type 1 diabetes was once known as juvenile-onset diabetes

because this condition is usually diagnosed in people under the

age of 20. Type 2 diabetes has also been called maturity-onset

diabetes, because it is usually diagnosed in people over the age of

40. The incidence of type 2 diabetes in children is rising (due to
    an increase in the frequency of obesity), however, so these terms
    are no longer preferred. The two forms of diabetes mellitus are
    compared in table  19.5. (It should be noted that only the early
    stages of type 1 and type 2 diabetes mellitus are compared; some
    people with severe type 2 diabetes may also require insulin injec-
    tions to control the hyperglycemia.)
    Diabetes is the major cause of kidney failure and limb
    amputations, and is the second leading cause of blindness. Fur-
    thermore, because type 2 diabetes is associated with metabolic
    syndrome (discussed in the Clinical Application box on p. 672),
    in which there is high blood triglycerides and low HDL choles-
    terol, there is increased risk of atherosclerosis. Thus, diabetes is
    also a significant contributor to heart disease and stroke.

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is an autoimmune disease (chapter 15,

section 15.6), and like other autoimmune diseases, the suscepti-

bility for it is associated with genes of the major histocompatabil-

ity complex (MHC) on chromosome 6. The risk of developing

type 1 diabetes mellitus is about 6% among siblings of a patient

with this disease; the risk rises to about 65% between identical

19.4 DIABETES MELLITUS

AND HYPOGLYCEMIA

Inadequate secretion or action of insulin produces metabolic

disturbances characteristic of diabetes mellitus. A person

with type 1 diabetes requires injections of insulin; a person

with type 2 diabetes can control this condition by other meth-

ods. A person with reactive hypoglycemia secretes excessive

amounts of insulin.

Figure 19.10 The effect of feeding and fasting on
metabolism. Metabolic balance is tilted toward anabolism by
feeding (absorption of a meal) and toward catabolism by fasting.
This occurs because of an inverse relationship between insulin
and glucagon secretion. Insulin secretion rises and glucagon
secretion falls during food absorption, whereas the opposite
occurs during fasting.

Insulin

Glucagon

Metabolism

Insulin/glucagon

ratio

Hydrolysis of

glycogen, fat,

and protein

+

Gluconeogenesis

and ketogenesis

Blood

Insulin

Glucagon

Formation of

glycogen, fat,

and protein

Blood

Absorption

of meal

( Glucose)

Fasting

( Glucose)

Insulin/glucagon

ratio

Glucose

Amino acids

Fatty acids

Ketone bodies

Glucose

Amino acids

Fatty acids

Ketone bodies

LEARNING OUTCOMES

After studying this section, you should be able to:

10. Distinguish between type 1 and type 2 diabetes
    mellitus.


11. Explain insulin resistance and impaired glucose
    tolerance, and describe hypoglycemia.

Chronic high blood glucose, or hyperglycemia, is the hallmark
of diabetes mellitus. The name of this disease is derived from
the fact that glucose “spills over” into the urine when the blood