Plasma Glucose HomeostasisWidmaier et al., p. 555-567

• Glucose metabolism

• Hormonal Control

• Disruptions of glucose homeostasis

• A Case Study

1QQ # 3 8:30 Section

1. Which of the following are true during the absorptive phase? (Circle all correct responses.)a) Amino acids are taken up by muscle tissue.b) The liver converts glucose to a-ketoacids.c) Muscle cells polymerize glucose to glycogen.d) Excess amino acids are converted to triglycerides in

the liver in a multi-stop enzymatic processe) As plasma glucose levels rise, so does the secretion

of insulin.f) Adipose tissue converts excess glucose to

triglycerides.g) Almost all cells use glucose as metabolic fuel.

1 a b c d e f g

1QQ # 3 9:30 Section

1. Which of the following are true during the absorptive phase? (Circle all correct responses.)a) Amino acids are released by muscle tissue.b) The liver converts glucose to a-ketoacids.c) Muscle cells polymerize glucose to glycogen.d) Excess amino acids are converted to triglycerides in

the liver in a multi-stop enzymatic processe) As plasma glucose levels rise, secretion of insulin is

diminished.f) Triglycerides enter adipose tissue cells.g) Almost all cells use fatty acids as their main

metabolic fuel.

1 a b c d e f g

Fig. 16.01

=sink

Abs

orpt

ive

Pha

se

Hepatic Portal System

Lipoprotein Lipase

Islets of Langerhans

Alpha cells secrete glucagonBeta cells secrete insulinDelta cells secrete somatostatin

Route of blood

LiverTypical vasculature: Artery-Arteriole-Capillary-Venule-Vein-Heart

Hepatic portal systemArtery-Arteriole-Capillary-Portal Vessel- Capillary-Venule-Vein-Heart

Fig. 16.02

Post-absorptive phase

Glucose Sparing

Special case: Muscle wasting of starvation

Note: Nervous tissuecan use glucose and ketones

Special term:Glycogenolysis &Gluconeogenesis

Major Points• Absorptive phase lasts ~ 4 hours, cells “burn” glucose.• During absorptive phase, energy needs provided by

recently digested food• During absorptive phase, excess is converted to

stored fuel• During post-absorptive phase, energy need met by

release of stored fuels, most cells “burn” fatty acids, nervous tissue uses glucose and ketones.

• Fasting defined as greater than 12 hours after previous meal (some say 24 hrs)

• Fasting for several days has little effect on plasma glucose levels

The Issues

• How do cells “know” which fuel to “burn?”• How do cells “know” when to synthesize

glycogen or lipids and when to break down glycogen or lipid?

• What is responsible for the transitions from the absorptive and post-absorptive states?

• How does glucose get into “sink” cells?

Fig. 16.07Identify sensors, afferent pathway,integrator,efferent pathway,effectors

How is insulin secretion affected if plasma glucose is lower than set point?

Which cell types have insulin receptors?

Activates some enzymes, inactivates others

GLUT-4

Peptide hormone

Exercise (via an undescribed mechanism) increases the number of glucose transporters in muscle cell membrane

Diabetes mellitus:T1DM =beta cells fail to produce adequate insulin (5%)T2DM = target cells “resistant” (less responsive) to insulin

↑ plasma glucose →↑insulin secretion→↑glucose uptake into cells →↓ plasma glucose

Stimulatory actions of insulin in green

Inhibitory actions of insulin in dashed red

Absorptive Phase

Post-Absorptive Phase

?

The Integrator integrates multiple inputs

Glucose uptake, Storage, Lipogenesis

WHY? FF

FF

Thinking about foodFactors that influence Insulin Secretion

Another hormone that regulates plasma glucose concentration

Glucagon prevails during post-absorptive phase

Transition from absorptive to post-absorptive phase?

Graph your daily caloric intake over a 48 hour period

6am 6am6pm 6pmNoon NoonMN MN

Cal

orie

sco

nsum

ed

6am Noon

PlasmaGlucose

100

65

Overlay INSULIN SECRETION on the graph

Overlay GLUCAGON SECRETION on the graph

Glucose-counterregulatory controls

(oppose effects of insulin)

GlucagonEpinephrineCortisol (permissive effect)Growth hormone (permissive effect)

Fig. 16.10

EPI, yet another horomone inglucose homeostasis, effects opposite of Insulin

Don’t fret about receptors, afferent pathway, and integrator for this feedback loop.

Who Cares?

A Case Study• On our website at• http://webs.wofford.edu/davisgr/bio342/oggt.htm

A Case Study of Glucose Homeostasis A 35 year old male presented with the following complaints: frequent severe headaches upon awakening at 4:30 am, blurred vision, and fatigue due to excessive stress at work. The patient complained of routine 16 hr workdays followed by a midnight snack of breakfast cereal. An OGTT was ordered and provided the following results: During the second hour of the OGTT, the patient exhibited anxiety, paleness, hunger, tremulousness, and cold sweat. No additional tests were ordered. The patient was instructed to replace the midnight snack of cereal with a protein-rich snack.

Oral Glucose Tolerance Test

• Overnight fast, no beverages other than water

• Fasting blood sample• Ingest 75 grams glucose• Blood samples every 0.5

hours for 3-5 hours• Plot plasma glucose

concentration over time• Compare curves Sugar content

of Red Bull?

60

Stress,Emergency (fight or flight)

Effect onBeta cells

Effect on Alpha Cells

The Answer to the Problem?

• Rationale for substituting protein for carbohydrate midnight snack?