Tissue uptake of glucose

Glucose enters the cells of most tissues by means of an active transport mechanism (section 3.2.2) that is stimulated by the hormone insulin. This means that insulin promotes the uptake and utilization of glucose in most tissues. After entry, glucose is phosphorylated to glucose 6-phosphate. In the liver, glucose enters cells by facilitated diffusion and is then trapped by phosphorylation to glucose 6-phosphate, which cannot cross cell membranes. Glucose 6-phosphate is then either metabolized as a metabolic fuel (section 5.4.1) or used to synthesize the storage carbohydrate glycogen (section 5.6.3).

Two enzymes catalyse the formation of glucose 6-phosphate from glucose:

  • Hexokinase is expressed in all tissues; it has a Km for glucose of 0.15 mmol/L.
  • Glucokinase is expressed only in liver and the P-cells of the pancreas; it has a Km for glucose of 20 mmol/L.

The normal range of plasma glucose is between 3.5 and 5 mmol/L, rising in peripheral blood to 8—10 mmol/L after a moderately high intake of glucose. The concentration of glucose in the portal blood, coming from the small intestine to the liver (section 4.2.2.3), may be considerably higher than this.

  • What effect do you think changes in the plasma concentration of glucose will have on the rate of formation of glucose 6-phosphate catalysed by hexokinase?
  • What effect do you think changes in the plasma concentration of glucose will have on the rate of formation of glucose 6-phosphate catalysed by glucokinase?
  • What do you think is the importance of glucokinase in the liver?

Froguel and co-workers (1993) reported studies of the glucokinase gene in a number of families affected by MODY and also in unaffected families. They published a list of 16 variants of the glucokinase gene, shown in Table 2.3. All their patients with MODY had an abnormality of the gene.

  • Using the genetic code shown in Table 9.8, fill in the amino acid changes associated with each mutation in the gene.
  • Why do you think the mutations affecting codons 4, 10 and 116 had no effect on the people involved?
  • What conclusions can you draw from this information?

The same authors also studied the secretion of insulin in response to glucose infusion in patients with MODY and normal control subjects. They were given an intravenous infusion of glucose; the rate of infusion was varied so as to maintain a constant plasma concentration of glucose of 10 mmol/L.

Table 2.3 Known mutations in the glucokinase gene

Codon

Nucleotide change

Amino acid change

Effect

4

GAC

AAC

?

None

10

GCC

GCT

?

None

70

GAA

AAA

?

MODY

98

CAG

TAG

?

MODY

116

ACC

ACT

?

None

175

GGA

AGA

?

MODY

182

GTG

ATG

?

MODY

186

CGA

TGA

?

MODY

203

GTG

GCG

?

MODY

228

ACG

ATG

?

MODY

261

GGG

AGG

?

MODY

279

GAG

TAG

?

MODY

300

GAG

AAG

?

MODY

300

GAG

CAG

?

MODY

309

CTC

CCC

?

MODY

414

AAG

GAG

?

MODY

From data reported by Froguel P et al. (1993) New England Journal of Medicine 328: 697—702.

From data reported by Froguel P et al. (1993) New England Journal of Medicine 328: 697—702.

Table 2.4 Plasma glucose and insulin before and after 60 minutes of glucose infusion in control subjects and patients with maturity-onset diabetes of the young (MODY)

Plasma glucose (mmol/L)

Insulin (mU/L)

Control

Control

Patients subjects

Patients

subjects

Fasting 7.0 ± 0.4 5.1 ± 0.3

5 ± 2

6 ± 2

Glucose infusion Maintained at 10 mmol/L

by varying rate of infusion

12 ± 7

40 ± 11

From data reported by Froguel P et al. (1993) New England Journal of Medicine 328: 697—702.

From data reported by Froguel P et al. (1993) New England Journal of Medicine 328: 697—702.

Their plasma concentrations of glucose and insulin were measured before and after 60 min of glucose infusion; the results are shown in Table 2.4.

  • What conclusions can you draw from this information about the probable role of glucokinase in the P-cells of the pancreas?
  • Can you deduce the way in which the P-cells of the pancreas sense an increase in plasma glucose and signal the secretion of insulin?
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment